- 3 Patients with PD-1 Refractory Cutaneous Melanoma are Responders Including One Complete Response (CR)
–
- Driven by Increased Prioritization of IMO-2125 Clinical Development, Company Suspends Development of
IMO-8400 for B-Cell Lymphomas –
CAMBRIDGE, Mass. and EXTON, Pa., Sept. 26, 2016 (GLOBE NEWSWIRE) -- 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 initial clinical data from its ongoing Phase 1/2 clinical trial of intra-tumoral IMO-2125, a Toll-like
receptor (TLR) 9 agonist. In this arm of the Phase 1 portion of the trial, IMO-2125 is being evaluated in combination with
ipilimumab for treatment of patients with metastatic melanoma who have failed prior PD-1 therapy. These early results
indicate that IMO-2125 is demonstrating promising clinical activity and is being well tolerated in a patient population with
minimal options and low expectation of clinical response with ipilimumab treatment alone. Further clinical information from
the ongoing dose escalation portion of the trial, as well as detailed information on the translational results, will be presented
during an oral session at the 2016 Society for Immunotherapy of Cancer Annual Meeting beginning November 9th in
Maryland.
“We have completed extensive pre-clinical work in a broad scope of tumor types to test the hypothesis of
intra-tumoral administration of IMO-2125 inducing a meaningful effect on the tumor microenvironment and potentiating local and
systemic tumor regression in patients. This work gave us confidence to test the ability of IMO-2125, beginning with this
current study in PD-1 refractory metastatic melanoma patients,” stated Vincent Milano, Idera’s Chief Executive Officer.
“We are energized by the early results from this ongoing trial and have been solidifying our plans to accelerate
the program as we believe there is a clear path to bring IMO-2125 to melanoma patients who have not benefited from checkpoint
inhibition alone and open an opportunity to establish IMO-2125 as the agent of choice to activate the tumor microenvironment and
potentially improve outcomes for patients,” Milano added. “Following a full strategic review, we have decided to prioritize
the IMO-2125 program and explore strategic options for IMO-8400 in B-cell lymphoma.”
Current Data Analysis
Safety
- 10 patients in 3 dosing cohorts (4mg, 8mg and 16mg) have been dosed and are assessable for safety, as of the September 19,
2016 cutoff date;
- IMO-2125 in combination with ipilimumab is being generally well tolerated at all 3 dose levels studied to date;
- Immune related adverse events have been observed in 3 subjects: 2 responding patients have experienced hypophysitis and 1
patient has discontinued the study due to a recurrence of immune related hepatitis previously observed on prior therapy with
ipilimumab;
- No dose limiting toxicities (DLTs) have been identified to date and the study is currently enrolling at the highest (32mg)
dosing cohort in combination with ipilimumab.
Clinical activity
- 6 patients treated in the first 2 dosing cohorts (4mg and 8mg) are assessable for initial clinical activity, as of the
September 19, 2016 cutoff date;
- 3 of the 4 patients with cutaneous melanoma are responders with one Complete Response (CR) and 2 Partial Responses (PR);
- 2 patients with mucosal melanoma experienced Progressive Disease (PD).
Translational observations
- Translational data seen through the first two dosing cohorts is promising relative to the induction of immune responses;
- Detailed information on the translational findings from biopsies taken in the first 2 dosing cohorts and the relationship of
these to clinical response is the subject of an accepted oral presentation on November 11, 2016 at the 2016 Society for
Immunotherapy of Cancer (SITC) Annual Meeting by Cara Haymaker, Ph.D., University of Texas, MD Anderson Cancer Center.
“The degree of activity we’ve seen so far in this trial is very exciting as these patients are very unlikely to
respond to other therapies. All three responses that we’ve seen are clinically meaningful, and these patients continue to do
well following treatment,” stated Adi Diab, M.D., Assistant Professor, Department of Melanoma Medical Oncology, Division of Cancer
Medicine, University of Texas, MD Anderson Cancer Center.
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 given intravenously. Following determination of the recommended Phase 2 dose (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. The primary
objective of the Phase 2 portion is to assess the clinical activity of IMO-2125 in combination with ipilimumab at the respective
RP2D in patients. 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 The University of Texas MD Anderson Cancer Center and is being led by Adi Diab, M.D., 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.
Business Update
Idera is also reporting that the company has chosen to suspend the clinical development of IMO-8400 for B-cell lymphomas, including
studies in Waldenstroms Macroglobulinemia (WM) and Diffuse Large B-Cell Lymphoma (DLBCL), and will explore strategic options in
these indications. This decision was based upon the prioritization of the clinical development plans for IMO-2125 and our
assessment that the level of clinical activity seen in the WM trial does not support monotherapy, the very slow enrollment rate in
DLBCL and our commercial assessment. No safety concerns have been observed with IMO-8400 in the B-cell Lymphoma program. The
development of IMO-8400 in dermatomyositis continues and is not impacted by this decision.
Investor Event and Webcast
Idera will host a conference call and live webcast on Monday, September 26 at 9:00 A.M. EST to review the data being presented
along with a discussion of the next steps for the IMO-2125 development program in melanoma. To participate in the conference
call, please dial (844) 882-7837 (domestic) and (574) 990-9824 (international). The webcast can be accessed live or in
archived form in the “Investor’s” section of the company’s website at www.iderapharma.com. The company has also posted a slide presentation to the Idera
corporate website in the “Investors” section which will be referenced during the conference call. Additionally the company
has updated its corporate presentation which has also been posted to the Idera corporate website in the “Investors” section.
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 agonist, IMO-2125 has been created using the company's proprietary chemistry-based discovery
platform. IMO-2125 has been shown 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 Melanoma
Melanoma 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 using a TLR-targeting technology, to design synthetic
oligonucleotide-based drug candidates to act by modulating the activity of specific TLRs. In addition to its TLR programs, Idera
has created a third generation antisense technology platform using its proprietary technology to inhibit the production of
disease-associated proteins by targeting RNA. To learn more about Idera, visit www.iderapharma.com.
Forward Looking Statements
This 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 the 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 June 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
