Key Publications

Oncology

AACR 2018 Annual Meeting, Chicago, IL, April 14-18, 2018

• Triple Combination of tilsotolimod, epacadostat, and anti PD 1 antibody demonstrates maximal tumor efficacy and eradicates large established tumors in preclinical models

SITC 2017 Annual Meeting, National Harbor, MD, November 8-12, 2017

• TLR9 Agonist Harnesses Innate Immunity Poster Presentation
• IMO-2125 SITC Oral Presentation

European Society for Medical Oncology 2017 Congress

• A Phase 1-2 Trial of Intratumoral IMO-2125 (IMO) in Combination with Checkpoint Inhibitors (CPI) in PD-(L)1-refractory Melanoma

Third Annual CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, Mainz, Germany, September 6-9, 2017

• Intratumoral IMO-2125 Treatment in Combination with Anti-CTLA-4 mAB Induces Durable Anti-tumor Responses Associated with Tumor-specific Memory in Preclinical Studies

AACR 2017 Annual Meeting, Washington, DC, April 1-5, 2017

• Translational evidence of reactivated innate and adaptive immunity with intratumoral IMO-2125 in combination with systemic checkpoint inhibitors from a Phase 1/2 study in patients with anti-PD-1 refractory metastatic melanoma
• Local treatment with novel TLR9 agonist IMO-2125 demonstrates antitumor activity in preclinical models of pancreatic cancer

OPT Boston 2017, Cambridge, MA, March 27-29, 2017

• Creating a Beneficial Tumor Microenvironment for Effective Cancer Immunotherapy

2017 ASCO-SITC Clinical Immuno-Oncology Symposium, Orlando, FL, February 23-25, 2017

• Intratumoral IMO-2125 a TLR9 Agonist is Active in Combination with Ipilimumab in PD-L(1) Refractory Melanoma

SITC 2016 Annual Meeting, National Harbor, MD, November 9-13, 2016

• IMO-2125 – An Investigational Intratumoral Toll-Like Receptor 9 Agonist Modulates the Tumor Microenvironment
• Reactivating the Anti-Tumor Response By Targeting Innate and Adaptive Immunity in a Trial of Intratumoral IMO-2125-oral presentation
• Reactivating the Anti-Tumor Response by Targeting Innate and Adaptive Immunity in a Trial of Intratumoral IMO-2125-poster

AACR 2016 Annual Meeting, New Orleans, LA, April 16-20, 2016

• Creating the tumor microenvironment for effective immunotherapy: Anti-tumor activity of intra-tumoral IMO-2125, a TLR9 agonist is further enhanced by inhibition of indoleamine-pyrrole 2,3-dioxygenase (IDO)

ASH 57th Annual Meeting & Exposition, Orlando, FL, December 5–8, 2015

• Interim Results From a Phase 1/2, Open-Label, Dose-Escalation Trial of IMO-8400 in Patients with Relapsed or Refractory Waldenstrom’s Macroglobulinemia

AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Boston, MA, November 5-9, 2015

• Intratumoral Administration of IMO-2125, a Novel TLR9 Agonist, Modulates Tumor Microenvironment and Potentiates Antitumor Activity of Anti-PD-1 mAb in Murine Colon Carcinoma and Melanoma Models

CRI-CIMT-EATI-AACR – The Inaugural International Cancer Immunotherapy Conference, New York, NY, September 16–19, 2015

• Intratumoral Administration of IMO-2125, a Novel TLR9 Agonist, Modulates the Tumor Microenvironment and Exerts Systemic Antitumor Activity Alone and in Combination with an Anti-CTLA-4 mAb
• Modulation of Checkpoint Expression in Tumor Microenvironment by Intratumoral Administration of a Novel TLR9 Agonist: Rationale for Combination Therapy

ASH 56th Annual Meeting & Exposition, San Francisco, CA, December 6–9, 2014

• Novel Approach to the Potential Treatment of Patients with B-cell Lymphomas Harboring the MYD88 L265P Mutation: Combination Treatment with TLR Antagonist and Rituximab
• IMO-8400, an Antagonist of Toll-like Receptors 7, 8, and 9, in Development for Genetically Defined B-cell Lymphomas: Safety and Tolerability in Phase 1 and Phase 2 Clinical Trials

ASH Meeting on Lymphoma Biology, Colorado Springs, CO, August 10–13, 2014

• Inhibition of TLR7 and TLR9 Blocks MYD88 L265P Oncogenic Mutation-mediated Signaling

AACR Annual Meeting, San Diego, CA, April 5–9, 2014

• IMO‐8400, a selective antagonist of TLRs 7, 8 and 9, inhibits MYD88 L265P mutation‐driven signaling and cell survival: A potential novel approach for treatment of B‐cell lymphomas harboring MYD88 L265P mutation

Rare Diseases

Brevard et al., Design Considerations for Clinical Trials Using the Cutaneous Dermatomyositis Disease Area and Severity Index as a Primary Endpoint. J Clin Exp Dermatol Res 2017, 8:4.

GCOM (Global Conference on Myositis), Potomac, MD, May 5-8, 2017

• Design of a Randomized, Double-Blind, Placebo Controlled Phase 2 Clinical Trial of the Toll-Like Receptor antagonist IMO-8400 in Patients with Dermatomyositis
• Analysis of Real-World Oral Prednisone Usage in Patients with Dermatomyositis Supports the Unmet Need for Additional Corticosteroid-Sparing Agents

MDA Scientific Conference 2017, Arlington, VA, March 19-22, 2017

• Design of a randomized, double-blind, placebo-controlled Phase 2 clinical trial of IMO-8400, a Toll-like receptor antagonist, in patients with dermatomyositis

MDA Scientific Conference 2015, Washington, DC, March 11–14, 2015

• Toll-like Receptor Antagonism as a Novel Anti-inflammatory Treatment Approach for Duchenne Muscular Dystrophy

8th International Workshop on Waldenström’s Macroglobulinemia and Symposium on Advances in Multiple Myeloma, London, U.K., August 13–17, 2014

• IMO-8400 Inhibits Tumor Growth and Signaling Pathways in Waldenström’s Macroglobulinemia: a Novel Therapeutic Approach in Development

Third-Generation Antisense

OPT Boston 2017, Cambridge, MA, March 27-29, 2017

• Third Generation Antisense (3GA) Technology: Insights into Mechanism of Action

The 12^th Annual Meeting of the Oligonucleotide Therapeutics Society, Montreal, Quebec, September 25 – 28, 2016

• Selective Targeting of Point Mutations by Third Generation Antisense (3GA) Oligonucleotides

• Third-generation antisense (3GA) targeting NLRP3 for the treatment of inflammatory disorders

Cold Spring Harbor Laboratory Conference on Regulatory & Non-Coding RNAs, Cold Spring Harbor, NY, August 23 – 27, 2016

• Precise excision of targeted RNA by third-generation antisense (3GA) oligonucleotides

Bhagat L, Putta MR, Wang D, Yu D, Lan T, Jiang W, Sun Z, Wang H, Tang JX, La Monica N, Kandimalla ER, Agrawal S. Novel oligonucleotides containing two 3′-ends complementary to target mRNA show optimal gene-silencing activity. J Med Chem. 2011 Apr 28;54(8):3027–36.

Yu D, Wang D, Zhu FG, Bhagat L, Dai M, Kandimalla ER, Agrawal S. Modifications incorporated in CpG motifs of oligodeoxynucleotides lead to antagonist activity of toll-like receptors 7 and 9. J Med Chem. 2009 Aug 27;52(16):5108–14.

Toll-Like Receptors

AAD Annual Meeting, San Francisco, CA, March 20–24, 2015

• Results from a randomized, double-blind, placebo-controlled, monotherapy trial of IMO-8400 demonstrate clinical proof-of-concept for Toll-like receptor 7, 8 and 9 antagonism in psoriasis

Digestive Disease Week, Washington DC, May 16–19, 2015

• Targeting Innate Immune Receptors to treat Inflammatory Bowel Disease: Activity of Oral IMO-9200, an antagonist of TLRs 7, 8, and 9, in mouse models of Colitis

10th Annual Meeting of the Oligonucleotide Therapeutics Society, San Diego, CA, October 12–15, 2014

• IMO-9200, A Novel Clinical-Stage TLR Antagonist for the Treatment of AutoImmune Diseases, Inhibits TLR-Mediated Immune Responses and Shows Activity in Animal Modes
• IMO-9200, A Novel Clinical-Stage TLR Antagonist for the Treatment of AutoImmune Diseases, Suppresses TLR-Mediated Immune in Non-Human Primates Following Systemic Administration

AACR Tumor Immunology and Immunotherapy Meeting, Orlando, FL, December 1–4, 2014

• Intratumoral injection of IMO‐2055, a novel Toll‐like receptor 9 agonist, with ipilimumab induces a systemic tumor‐specific immune response

ACR/ARHP Annual Meeting, San Diego, CA, October 25–30, 2013

• Treatment of psoriasis patients with IMO-3100 shows improvement in gene expression patterns of meta-analysis derived-3 transcriptome and IL-17 pathway

FOCIS 2013, Cambridge, MA, June 27–30, 2013

• Phase 1 clinical trial of IMO-8400, an antagonist of Toll-like receptors 7, 8, and 9

International Investigative Dermatology, Edinburgh, Scotland, May 8–11, 2013

• IMO-3100, an antagonist of Toll-like receptor (TLR) 7 and TLR9, demonstrates clinical activity in psoriasis patients with 4 weeks of treatment in a Phase 2a trial

AAD Annual Meeting, Miami Beach, FL, March 1–5, 2013

• Novel Toll-Like receptor antagonists strongly decrease expression of IL-23-induced and psoriasis profile genes in a mouse model

ACR/ARHP Annual Meeting, Washington, DC, November 9–14, 2012

• A selective inhibitor of endosomal Toll-Like receptors, IMO-8400, suppresses activation of multiple cytokines, Th17 response and inflammasome activation

Immunology 2012 AAI Conference, Boston, MA, May 4–8, 2012

• IMO-8400, a novel TLR7, TLR8 and TLR9 antagonist, inhibits disease development in mouse models of psoriasis

Suárez-Fariñas M, Arbeit R, Jiang W, Ortenzio FS, Sullivan T, Krueger JG. Suppression of molecular inflammatory pathways by Toll-like receptor 7, 8, and 9 antagonists in a model of IL-23-induced skin inflammation. PLoS ONE. 2013 Dec 27;8(12):e84634.

Kandimalla ER, Bhagat L, Wang D, Yu D, Sullivan T, La Monica N, Agrawal S. Design, synthesis and biological evaluation of novel antagonist compounds of Toll-like receptors 7, 8 and 9. Nucleic Acids Res. 2013 Apr 1;41(6):3947–61.

Jiang W, Zhu FG, Bhagat L, Yu D, Tang JX, Kandimalla ER, La Monica N, Agrawal S. A Toll-like receptor 7, 8, and 9 antagonist inhibits Th1 and Th17 responses and inflammasome activation in a model of IL-23-induced psoriasis. J Invest Dermatol. 2013 Jul;133(7):1777–84.

Zhu FG, Jiang W, Bhagat L, Wang D, Yu D, Tang JX, Kandimalla ER, La Monica N, Agrawal S. A novel antagonist of Toll-like receptors 7, 8 and 9 suppresses lupus disease-associated parameters in NZBW/F1 mice. Autoimmunity. 2013 Nov;46(7):419–28.

Wang D, Bhagat L, Yu D, Zhu FG, Tang JX, Kandimalla ER, Agrawal S. Oligodeoxyribonucleotide-based antagonists for Toll-like receptors 7 and 9. J Med Chem. 2009 Jan 22;52(2):551–8.

Yu D, Zhao Q, Kandimalla ER, Agrawal S. Accessible 5′-end of CpG-containing Phosphorothioate Oligodeoxynucleotides is Essential for Immunostimulatory Activity. Bioorg Med Chem Lett. 2000 Jul;10:2585–8.