cobomarsen (MRG-106) / Viridian Therap - LARVOL DELTA

Targeted inhibition of MDSC-derived exosomal miR-155-5p restrains epithelial-mesenchymal transition in hormone receptor-positive breast cancer by regulating SIRT1. (PubMed, Mater Today Bio) - "To address this, we developed a TME-responsive polymeric micelle co-delivering alpelisib (a pan-PI3K inhibitor) and cobomarsen (a miR-155-5p inhibitor) for targeted therapy. This dual-targeting strategy effectively suppressed PIK3CA-mutated tumor growth and epithelial-mesenchymal transition. These findings reveal the role of MDSC-driven metastatic potential via the exosomal miR-155-5p/SIRT1 axis in HR + breast cancer and present a novel nanotherapeutic approach for precision intervention."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • MIR155 • PIK3CA • SIRT1

Metabolic disorders affecting the liver and heart: therapeutic efficacy of miRNA-based therapies? (PubMed, Pharmacol Res) - "Finally, we sought to address research questions related to efficacy, side-effects, and range of use of RNA therapeutics. Additionally, we covered hurdles and examined recent advances in the use of miRNA-based RNA therapy in metabolic disorders such as diabetes, liver, and heart diseases."

Journal • Review • Cardiovascular • Diabetes • Heart Failure • Hepatology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

MicroRNA-based therapeutics for inflammatory disorders of the microbiota-gut-brain axis. (PubMed, Pharmacol Res) - "With increasing evidence of the pathophysiological importance for miRNAs in microbiota-gut-brain axis disorders, therapeutic targeting of cross-regulated miRNAs in these disorders displays potentially transformative and translational potential. Further preclinical research and human clinical trials are required to further advance this area of research."

Journal • Review • CNS Disorders • Gastrointestinal Disorder • Inflammation • Mental Retardation • Psychiatry

Ph 1 study of MRG-106, an inhibitor of miR-155, in CTCL. (ASCO 2018) - P1; "These preliminary results suggest that MRG-106 is well-tolerated, has clinical activity, and has potential to impact MF quality of life. These encouraging data support the continued investigation of MRG-106 in this population. The study is expanded to enroll pts with other hematologic malignancies in which miR-155 is elevated and relevant, including CLL, DLBCL, ATLL."

Chronic Lymphocytic Leukemia • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Indolent Lymphoma

Emerging drugs for the treatment of cutaneous T-cell lymphoma. (PubMed, Expert Opin Emerg Drugs) - "Mogamulizumab and brentuximab vedotin have reached the market and are approved for the treatment of CTCL, providing valuable options. Durvalumab, pembrolizumab, TTI-621, BNZ-1, and MRG-106 are several of the emerging treatments still in trials. Further combinatorial studies are needed as none of the treatments have demonstrated long term remissions."

Journal • Cutaneous T-cell Lymphoma • Dermatopathology • Hematological Malignancies • Immune Modulation • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Ph 1 study of MRG-106, an inhibitor of miR-155, in CTCL. (ASCO 2018) - P1; "These preliminary results suggest that MRG-106 is well-tolerated, has clinical activity, and has potential to impact MF quality of life. These encouraging data support the continued investigation of MRG-106 in this population. The study is expanded to enroll pts with other hematologic malignancies in which miR-155 is elevated and relevant, including CLL, DLBCL, ATLL."

Chronic Lymphocytic Leukemia • Cutaneous T-cell Lymphoma • Diffuse Large B Cell Lymphoma • Indolent Lymphoma

Targeted eicosanoids profiling reveals a prostaglandin reprogramming in breast Cancer by microRNA-155. (PubMed, J Exp Clin Cancer Res) - "Considering clinical trials targeting PGE2 production largely have focused on the inhibition of Cox1 or Cox2 that showed cardiac toxicity, our data suggest an alternative way for suppressing PGE2 production via the inhibition of miR-155. As the antagomiR of miR-155 (MRG-106) underwent a phase-1 clinical trial, its effect should be considered and analyzed in prostaglandin metabolism in tumor."

Journal • Breast Cancer • Immunology • Inflammation • Oncology • Solid Tumor • Triple Negative Breast Cancer • KLF4 • MIR155 • MYC

SOLAR: Efficacy and Safety of Cobomarsen (MRG-106) vs. Active Comparator in Subjects With Mycosis Fungoides (clinicaltrials.gov) - P2; N=37; Terminated; Sponsor: miRagen Therapeutics, Inc.; N=126 ➔ 37; Trial completion date: Mar 2022 ➔ Dec 2020; Active, not recruiting ➔ Terminated; Trial primary completion date: Apr 2021 ➔ Oct 2020; The study was terminated early for business reasons, and not due to concerns regarding safety or lack of efficacy.

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Safety, Tolerability and Pharmacokinetics of MRG-106 in Patients With Mycosis Fungoides (MF), CLL, DLBCL or ATLL (clinicaltrials.gov) - P1; N=66; Completed; Sponsor: miRagen Therapeutics, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Chronic Lymphocytic Leukemia • Cutaneous T-cell Lymphoma • Dermatology • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Cobomarsen, an oligonucleotide inhibitor of miR-155, slows DLBCL tumor cell growth in vitro and in vivo. (PubMed, Clin Cancer Res) - "Our findings support the potential therapeutic application of cobomarsen in ABC-DLBCL and other types of lymphoma with elevated miR-155 expression."

Journal • Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

PRISM: Efficacy and Safety of Cobomarsen (MRG-106) in Subjects With Mycosis Fungoides Who Have Completed the SOLAR Study (clinicaltrials.gov) - P2; N=8; Terminated; Sponsor: miRagen Therapeutics, Inc.; N=60 ➔ 8; Trial completion date: Dec 2022 ➔ Jul 2020; Enrolling by invitation ➔ Terminated; Trial primary completion date: Dec 2021 ➔ Jul 2020; Study no longer needed because eligible subjects may receive treatment with cobomarsen in a crossover arm of the SOLAR clinical trial (NCT03713320)

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

miRagen Announces Internal Review of Preliminary Topline Data for the Phase 2 SOLAR Clinical Trial of Cobomarsen in Patients with Cutaneous T-Cell Lymphoma (CTCL) (GlobeNewswire) - P2, N=126; SOLAR (NCT03713320); Sponsor: miRagen Therapeutics; "Based on investigator assessments, these preliminary data in 37 patients suggest that cobomarsen lacks a compelling result for the study's primary endpoint, objective skin response of at least four months duration (ORR4) relative to the vorinostat control arm. Progression free survival (PFS), a secondary endpoint for the study, indicates a treatment effect in favor of cobomarsen. In addition, cobomarsen was well tolerated, with no patient discontinuations due to cobomarsen-related adverse events."

P2 data • Cutaneous T-cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

miRagen Announces Results of Meeting With FDA Regarding the Design of Pivotal Trial for Cobomarsen in ATLL (GlobeNewswire) - "miRagen Therapeutics...announced that the company held a Type C meeting with the FDA Office of Oncologic Diseases on August 11, 2020 to discuss miRagen’s future clinical development plans for cobomarsen for the potential treatment of Adult T-Cell Leukemia/Lymphoma (ATLL)....'With additional cobomarsen data from the ongoing Phase 2 SOLAR trial in Cutaneous T-cell lymphoma (CTCL) patients expected before the end of the year, we will be able to determine next steps for this program, which may include seeking a partner for the late-stage development and potential commercialization of cobomarsen in miR-155 elevated cancers including CTCL and ATLL' said William S. Marshall, Ph.D., miRagen’s President and Chief Executive Officer." "

FDA event • P2 data • Cutaneous T-cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

miR-155 as a novel clinical target for hematological malignancies. (PubMed, Carcinogenesis) - "This, together with increasing understanding of its key targets in cancer and the use of powerful mouse models of miR-155 in cancer, makes miR-155 an ideal target for therapeutic inhibition. Here, we review the role of miRNAs, and particularly miR-155, in cancers, and discuss progress on therapeutically targeting it, including the ongoing clinical trial of anti-miR-155 molecule Cobomarsen (MRG-106)."

Clinical • Journal • Hematological Disorders • Hematological Malignancies • Immunology • Oncology

miRagen Reports Second Quarter 2020 Financial Results and Provides Business Updates (Miragen Therapeutics Press Release) - "Cobomarsen: Cobomarsen is currently being evaluated for the potential treatment of patients with miR-155 elevated hematological malignancies, including Cutaneous T-Cell Lymphoma (CTCL) and Adult T-Cell Leukemia/Lymphoma (ATLL)....Based on the clinical data released earlier this year, during the second quarter of 2020, the Company requested a meeting with the FDA to discuss the development path for cobomarsen in ATLL and plans to meet with the FDA and receive guidance on the Company’s proposed clinical path in this indication before the end of 2020."

FDA event • Cutaneous T-cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Cobomarsen Receives Orphan Drug Designation From the U.S. FDA for the Treatment of T-cell Lymphoma (GlobeNewswire) - "miRagen Therapeutics...announced that the Food & Drug Administration (FDA) has granted orphan drug designation to cobomarsen, for the treatment of T-cell lymphoma. Cobomarsen is an inhibitor of miR-155 currently being developed by miRagen in two clinical programs to address different types of T-cell lymphoma, including a Phase 2 trial for cutaneous T-cell lymphoma (CTCL) and a Phase 1 trial for adult T-cell leukemia/lymphoma (ATLL)."

Orphan drug • Cutaneous T-cell Lymphoma • Hematological Malignancies • Oncology

Miragen Therapeutics to present new cobomarsen phase 1 clinical trial data at the 2018 American Society of Hematology Annual Meeting (GlobeNewswire) - P1, N=NA; "miRagen Therapeutics...today announced that new data from its Phase 1 trial of cobomarsen, an inhibitor of miR-155, in patients with mycosis fungoides, the most common form of cutaneous T cell lymphoma, will be presented at the 60th American Society of Hematology (ASH) Annual Meeting, which is being held in San Diego, CA, from December 1st – 4th."

P1 data • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Phase 1 Trial of Cobomarsen, an Inhibitor of Mir-155, in Cutaneous T Cell Lymphoma (ASH 2018) - "Background :Cobomarsen (MRG-106) is an inhibitor of miR-155, a microRNA with a strong link to cutaneous T cell lymphoma (CTCL) pathogenesis...The study is expanded to enroll patients with other hematologic malignancies in which miR-155 is elevated and relevant, including chronic lymphocytic leukemia (CLL), diffuse large B cell lymphoma (DLBCL), and adult T cell lymphoma/leukemia (ATLL). Final safety and efficacy data on CTCL mycosis fungoides will be presented."

P1 data • Biosimilar • Chronic Lymphocytic Leukemia • CNS Disorders • Cutaneous T-cell Lymphoma • Dermatology • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain

miRagen Therapeutics to present new cobomarsen clinical trial data for adult T-Cell leukemia/lymphoma and cutaneous T-Cell lymphoma at the 11th annual T-Cell lymphoma forum (GlobeNewswire) - "miRagen Therapeutics...announced that it will present new data from its Phase 1 trial of cobomarsen in HTLV-1 associated adult T-cell leukemia/lymphoma (ATLL) as well as its Phase 1 trial of cobomarsen in patients with mycosis fungoides, the most common form of cutaneous T-cell (CTCL) at the 11th Annual T-Cell Lymphoma Forum, which is being held in La Jolla, CA, from January 10th-12th."

P1 data • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

"Christians Querfeld next presented an update on the phase 1 trial of MRG106 in MF" (@ahalvani)

P1 data • Biosimilar

miRagen Therapeutics to present new interim data from phase 1 clinical trial of cobomarsen at the 2018 American Society of Clinical Oncology Annual Meeting (GlobeNewswire) - P1, N=75; NCT02580552; "miRagen Therapeutics...announced today that new interim data from its ongoing Phase 1 clinical trial of cobomarsen (also known as MRG-106) in patients with the mycosis fungoides form of cutaneous T-cell lymphoma (CTCL) will be presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting...In addition, preliminary observations on the safety and efficacy in adult T-cell leukemia/lymphoma (ATLL) patients dosed with cobomarsen will be presented."

P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

miRagen reports first quarter 2020 financial results and provides corporate update (Miragen Therapeutics Press Release) - "The Company is actively monitoring the effects of the COVID-19 pandemic on the SOLAR trial but cannot predict at this time when it will be able to collect uninterrupted endpoint data, with consistent dosing....Accordingly, the Company no longer expects to report topline data from the SOLAR trial in the third quarter of 2020....Based on these results, the Company announced that it is focusing its cobomarsen expansion indication efforts on ATLL and expects to request a meeting with the FDA in the second quarter of 2020 to explore a potential expedited development path for cobomarsen in ATLL. Under normal circumstances, the Company would expect to meet with the FDA in the third quarter of 2020. However, as the FDA prioritizes its efforts on COVID-19, it is uncertain if the meeting will occur on the standard FDA timeline. The Company therefore cannot provide assurances that the meeting will occur as originally expected in the third quarter of 2020."

FDA event • P3 data • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

SOLAR: Efficacy and Safety of Cobomarsen (MRG-106) vs. Active Comparator in Subjects With Mycosis Fungoides (clinicaltrials.gov) - P2; N=126; Active, not recruiting; Sponsor: miRagen Therapeutics, Inc.; Recruiting ➔ Active, not recruiting

Enrollment closed

Miragen reports fourth quarter and full year 2019 financial results (Miragen Therapeutics Press Release) - P2, N=126; SOLAR (NCT03713320); Sponsor: miRagen Therapeutics; "Completed enrollment of 37 patients in the Phase 2 SOLAR trial of cobomarsen in CTCL; expects to report topline data in Q3 2020....Completed initial planned enrollment of the Phase 1 trial of cobomarsen in ATLL patients; reported additional data in January 2020; expects to meet with the FDA in Q3 2020 to explore a potential expedited development path."

FDA event • P2 data

Safety, Tolerability and Pharmacokinetics of MRG-106 in Patients With Mycosis Fungoides (MF), CLL, DLBCL or ATLL (clinicaltrials.gov) - P1; N=75; Active, not recruiting; Sponsor: miRagen Therapeutics, Inc.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed