Delving into the Latest Updates on Danvatirsen with Synapse

Overview

Basic Info

Drug Type

ASO

Synonyms

Danvatirsen-sodium, IONIS-STAT3RX, ISIS-STAT3RX

+ [9]

Target

STAT3

Action

inhibitors

Mechanism

STAT3 inhibitors(Signal transducer and activator of transcription 3 inhibitors)

Therapeutic Areas

NeoplasmsNervous System DiseasesCongenital Disorders+ [6]

Active Indication

Advanced Colorectal AdenocarcinomaAdvanced Lung Non-Small Cell CarcinomaColorectal Cancer, Hereditary Nonpolyposis, Type 1+ [12]

Inactive Indication

Advanced cancerAdvanced Hepatocellular CarcinomaDiffuse Large B-Cell Lymphoma+ [3]

Originator Organization

Ionis Pharmaceuticals, Inc.

Active Organization

AstraZeneca PLC

Flamingo Therapeutics BV

Inactive Organization

Ionis Pharmaceuticals, Inc.

MedImmune LLC

Dynacure SA

License Organization

Ionis Pharmaceuticals, Inc.

Eli Lilly & Co.

AstraZeneca PLC

+ [1]

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

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Sequence Code 526076414

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Open-label, Phase II, randomized, controlled study evaluating the efficacy and safety of danvatirsen in combination with pembrolizumab compared with pembrolizumab alone as first-line treatment of patients with recurrent/metastatic (R/M) HNSCC. Two-thirds of patients will be randomized to receive danvatirsen and pembrolizumab and one-third will be randomized to receive pembrolizumab alone.

Start Date30 May 2023

Sponsor / Collaborator

Flamingo Therapeutics BV

NCT03794544

/ CompletedPhase 2

A Phase 2 Open-label, Multicenter, Randomized, Multidrug Platform Study of Neoadjuvant Durvalumab Alone or in Combination With Novel Agents in Subjects With Resectable, Early-stage (I [> 2 cm] to IIIA) Non-small Cell Lung Cancer (NeoCOAST)

Study D9108C00002 (NeoCOAST) is a platform study assessing the effectiveness and safety of neoadjuvant durvalumab alone or in combination with novel agents in participants with resectable, early-stage (Stage I [>2cm] to IIIA) non-small cell lung cancer (NSCLC).

Start Date08 Mar 2019

Sponsor / Collaborator

MedImmune LLC

100 Clinical Results associated with Danvatirsen

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100 Translational Medicine associated with Danvatirsen

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100 Patents (Medical) associated with Danvatirsen

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18

Literatures (Medical) associated with Danvatirsen

01 May 2025·Immunity Inflammation and Disease

Oligonucleotide‐Based Modulation of Macrophage Polarization: Emerging Strategies in Immunotherapy

Review

Author: Zhang, Hanfu ; Qian, Cheng ; Yu, Yizhi

ABSTRACT:

Background:

Recent advances in immunotherapy have spotlighted macrophages as central mediators of disease treatment. Their polarization into pro‑inflammatory (M1) or anti‑inflammatory (M2) states critically influences outcomes in cancer, autoimmunity, and chronic inflammation. Oligonucleotides have emerged as highly specific, scalable, and cost‑effective agents for reprogramming macrophage phenotypes.

Objective:

To review oligonucleotide strategies—including ASOs, siRNAs, miRNA mimics/inhibitors, and aptamers—for directing macrophage polarization and their therapeutic implications.

Review Scope:

We examine key signaling pathways governing M1/M2 phenotypes, describe four classes of oligonucleotides and their mechanisms, and highlight representative preclinical and clinical applications.

Key Insights:

Agents such as AZD9150, MRX34, and AS1411 demonstrate macrophage reprogramming in cancer, inflammation, and infection models. Advances in ligand‑conjugated nanoparticles and chemical modifications improve delivery and stability, yet immunogenicity, off‑target effects, and formulation challenges remain significant barriers.

Future Perspectives:

Optimizing delivery platforms, enhancing molecular stability, and rigorous safety profiling are critical. Integration with emerging modalities—such as engineered CAR‑macrophages—will enable precise, disease‑specific interventions, and advance oligonucleotide‑guided macrophage modulation toward clinical translation.

01 Apr 2025·MedComm

STAT3 Signaling Pathway in Health and Disease

Review

Author: Tabrez, Shams ; Alhashmi, Mohammad Hassan ; Samad, Md Abdus ; Ahmad, Iftikhar ; Hasan, Aakifah ; Al‐Abbasi, Fahad A. ; Ayub, Arusha ; Kumer, Ajoy

ABSTRACT:

Signal transducer and activator of transcription 3 (STAT3) is a critical transcription factor involved in multiple physiological and pathological processes. While STAT3 plays an essential role in homeostasis, its persistent activation has been implicated in the pathogenesis of various diseases, particularly cancer, bone‐related diseases, autoimmune disorders, inflammatory diseases, cardiovascular diseases, and neurodegenerative conditions. The interleukin‐6/Janus kinase (JAK)/STAT3 signaling axis is central to STAT3 activation, influencing tumor microenvironment remodeling, angiogenesis, immune evasion, and therapy resistance. Despite extensive research, the precise mechanisms underlying dysregulated STAT3 signaling in disease progression remain incompletely understood, and no United States Food and Drug Administration (USFDA)‐approved direct STAT3 inhibitors currently exist. This review provides a comprehensive evaluation of STAT3's role in health and disease, emphasizing its involvement in cancer stem cell maintenance, metastasis, inflammation, and drug resistance. We systematically discuss therapeutic strategies, including JAK inhibitors (tofacitinib, ruxolitinib), Src Homology 2 domain inhibitors (S3I‐201, STATTIC), antisense oligonucleotides (AZD9150), and nanomedicine‐based drug delivery systems, which enhance specificity and bioavailability while reducing toxicity. By integrating molecular mechanisms, disease pathology, and emerging therapeutic interventions, this review fills a critical knowledge gap in STAT3‐targeted therapy. Our insights into STAT3 signaling crosstalk, epigenetic regulation, and resistance mechanisms offer a foundation for developing next‐generation STAT3 inhibitors with greater clinical efficacy and translational potential.

01 Jul 2024·BMJ Oncology

Preclinical study and parallel phase II trial evaluating antisense STAT3 oligonucleotide and checkpoint blockade for advanced pancreatic, non-small cell lung cancer and mismatch repair-deficient colorectal cancer

Article

Author: Couillault, Coline ; Tang, Chad ; Piha-Paul, Sarina A ; Pant, Shubham ; Karp, Daniel D ; Dai, James ; Nicholas, Courtney ; Hartley, Genevieve P ; Proia, Theresa ; Yuan, Ying ; Dhebat, Sarah ; Fu, Siqing ; Curran, Michael A ; Lin, Heather ; Yap, Timonthy A ; Hong, David S ; Subbiah, Vivek ; Tsimberidou, Apostolia M ; Guerrero, Paola ; Srinivasamani, Anupallavi ; Dumbrava, Ecaterina E Ileana ; Naing, Aung ; Rodon Ahnert, Jordi

Objective:

To evaluate signal transducer and activator of transcription 3 (STAT3) inhibition we conducted a co-clinical trial testing danvatirsen, a STAT3 antisense oligonucleotide (ASO) and checkpoint inhibition in conjunction with preclinical experiments.

Methods and analysis:

Orthotopically implanted pancreatic cancer (pancreatic adenocarcinoma (PDAC)) was treated with STAT3 ASO with immune checkpoint inhibition. Tumour infiltrating immune cell populations were characterised via flow cytometry. In vitro experiments evaluated STAT3 inhibition in pancreatic stellate cells (PSCs) and myeloid-derived suppressor cells (MDSCs).A phase II trial employing a Simon II stage design tested the clinical efficacy of danvatirsen and durvalumab in non-small cell lung cancer (NSCLC), PDAC and mismatch repair-deficient colorectal cancer (MRD CRC). The primary objective was 4-month disease control rate (DCR).

Results:

In vivo studies identified improvement in survival of PDAC implanted mice treated with STAT3 ASO and checkpoint inhibition. Within tumour-infiltrating lymphocytes there was expansion of CD4 and PD-1+ CD8 populations with STAT3 ASO.Thirty-seven patients (29 PDAC, 7 NSCLC and 1 MRD CRC) from a single institution started treatment on trial between April 2017 and March 2020. No objective responses were observed. Four of six (66.7%, 95% CI 22.3% to 95.7%) NSCLC and 4 of 23 (17.4%, 95% CI 5% to 38.8%) PDAC patients exhibited 4-month DCR. Follow-up in vitro studies revealed an anti-inflammatory and pro-tumour effect of STAT3 ASO mediated by PSCs and MDSCs distinct from ablation of STAT3.

Conclusion:

Although durvalumab and danvatirsen met the primary endpoint, no objective responses were observed. A rationale for the lack of objective responses is danvatirsen-induced myeloid immune suppression.

Trial registration number:

NCT02983578 .

25

News (Medical) associated with Danvatirsen

15 Apr 2025

·flamingotx.com

Flamingo Therapeutics Announces Poster Presentation on the Immune-Modulatory Effects of Danvatirsen at the American Association for Cancer Research (AACR) Annual Meeting - Flamingo Therapeutics

Flamingo Therapeutics Announces Poster Presentation on the Immune-Modulatory Effects of Danvatirsen at the American Association for Cancer Research (AACR) Annual Meeting Leuven (Belgium), Strasbourg (France), Philadelphia (USA) – April 15, 2025 /PRNewswire/- Flamingo Therapeutics (“Flamingo”) today announced that an abstract has been accepted for presentation at the American Association for Cancer Research (AACR) annual meeting being held in Chicago, IL from April 25-30, 2025. Poster presentation details are as follows: Poster Title: “ASO-mediated STAT3 knockdown relieves immunosuppression sensitizing tumors to immunotherapies” Session Category/Title: Immunology/Modulation of Tumor Microenvironment: Enhancing Immunogenicity and Counteracting Suppression Session Time: 4/28/2025 9:00:00 AM - 12:00:00 PM Location: Poster Section 38 Published Abstract Number: 2244 For more information, please visit the AACR Annual Meeting 2025 website. About Flamingo Therapeutics Flamingo is pioneering RNA-targeted therapies for oncology with a clinical-stage pipeline targeting undruggable transcription factors and long non-coding RNAs. Flamingo has an alliance with Ionis Pharmaceuticals and is supported by well-known biotechnology investors including Abrdn (formerly funds managed by Tekla Capital Management LLC), Andera Partners, Bpifrance Large Venture, Bpifrance through its FABS and Fonds Biothérapies Innovantes et Maladies Rares funds, Eurazeo - Kurma Partners, Perceptive Advisors, PMV, Pontifax, Sphera, and VIB. Flamingo has initiated a Phase II trial ‘PEMDA-HN’ evaluating the STAT3 targeting agent danvatirsen, in combination with pembrolizumab, in patients with head and neck squamous cell carcinoma (HNSCC). A Phase I investigator initiated trial study has also been initiated evaluating danvatirsen as a monotherapy and in combination with venetoclax in AML/MDS patients. For more information on Flamingo, please visit: https://flamingotx.com PEMDA-HN (head and neck cancer) on clinicaltrials.gov: https://clinicaltrials.gov/study/NCT05814666 Danvatirsen monotherapy followed by combination with venetoclax in relapsed/ refractory AML and MDS on clincaltrials.gov: https://classic.clinicaltrials.gov/ct2/show/NCT05986240 Please engage with us on LinkedIn: https://www.linkedin.com/company/flamingo-therapeutics. Flamingo Media and Investor Contact: Amy Conrad Juniper Point (858) 366-3243 amy@juniper-point.com

ImmunotherapyAACRPhase 2Phase 1

04 Dec 2024

·www.prnewswire.com

Flamingo Therapeutics Announces Poster Presentation on AML Phase 1 IIT Study at ASH 2024

LEUVEN, Belgium and STRASBOURG, France and PHILADELPHIA, Dec. 4, 2024 /PRNewswire/ -- Flamingo Therapeutics ("Flamingo") today announced that an abstract has been selected for presentation at the 66th Annual ASH Annual Meeting and Exposition, being held in San Diego, CA from December 7-9, 2024. The abstract, selected for a poster presentation, is a Trials-in-Progress presentation of a Phase 1 investigator-initiated study of danvatirsen monotherapy followed by danvatirsen combination with venetoclax in relapsed/refractory AML and intermediate/high risk MDS (NCT05986240). The study is being conducted at Albert Einstein / Montefiore Medical Center in New York City and MD Anderson Cancer Center in Houston. Poster presentation details are as follows: Title: "A Phase 1 Study Investigating the Safety and Efficacy of Danvatirsen As Monotherapy Followed by Combination with Venetoclax in Patients with Relapsed/Refractory MDS and AML" Session Date: Monday, December 9, 2024 Presenting Author: Dr. Aditi Shastri For more information, please visit the ASH 2024 website. About Flamingo Therapeutics Flamingo is pioneering RNA-targeted therapies for oncology with a clinical-stage pipeline targeting undruggable transcription factors and long non-coding RNAs. Flamingo has an alliance with Ionis Pharmaceuticals and is supported by well-known biotechnology investors including Abrdn (formerly funds managed by Tekla Capital Management LLC), Andera Partners, Bpifrance Large Venture, Bpifrance through its FABS and Fonds Biothérapies Innovantes et Maladies Rares funds, Eurazeo - Kurma Partners, Perceptive Advisors, PMV, Pontifax, Sphera, and VIB. Flamingo has initiated a Phase II trial 'PEMDA-HN' evaluating the STAT3 targeting agent danvatirsen, in combination with pembrolizumab, in patients with head and neck squamous cell carcinoma (HNSCC). A Phase I investigator initiated trial study has also been initiated evaluating danvatirsen as a monotherapy and in combination with venetoclax in AML/MDS patients. For more information on Flamingo, please visit: PEMDA-HN (head and neck cancer) on clinicaltrials.gov: Danvatirsen monotherapy followed by combination with venetoclax in relapsed/ refractory AML and MDS on clincaltrials.gov: Please engage with us on LinkedIn: . Flamingo Media and Investor Contact: Amy Conrad Juniper Point (858) 366-3243 [email protected] SOURCE Flamingo Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 1Phase 2AACRsiRNA

29 Aug 2024

·www.prnewswire.com

Flamingo Therapeutics Announces Participation in Upcoming Investor Conferences

LEUVEN, Belgium and STRASBOURG, France and PHILADELPHIA, Aug. 29, 2024 /PRNewswire/ -- Flamingo Therapeutics ("Flamingo") announced today its participation in the following upcoming investor conferences: Wells Fargo Annual Healthcare Conference, September 4-6, 2024, Boston, MA PA Life Sciences Future Conference, September 18-19, 2024, Philadelphia, PA 8th Annual Chardan Genetic Medicines Conference, September 30-October 1, 2024, NY 4th Annual Needham Private Biotech Company Virtual 1x1 Forum, October 8-9, 2024 During these events, Company management will participate in one-on-one meetings with investors. About Flamingo Therapeutics Flamingo is pioneering RNA-targeted therapies for oncology with a clinical-stage pipeline targeting undruggable transcription factors and long non-coding RNAs. Flamingo has an alliance with Ionis Pharmaceuticals and is supported by well-known biotechnology investors including Abrdn (formerly funds managed by Tekla Capital Management LLC), Andera Partners, Bpifrance Large Venture, Bpifrance through its FABS and Fonds Biothérapies Innovantes et Maladies Rares funds, Eurazeo - Kurma Partners, Perceptive Advisors, PMV, Pontifax, Sphera, and VIB. Flamingo has initiated a Phase II trial 'PEMDA-HN' evaluating the STAT3 targeting agent danvatirsen, in combination with pembrolizumab, in patients with head and neck squamous cell carcinoma (HNSCC). A Phase I investigator initiated trial study has also been initiated evaluating danvatirsen as a monotherapy and in combination with venetoclax in AML/MDS patients. For more information on Flamingo, please visit: PEMDA-HN (head and neck cancer) on clinicaltrials.gov: Danvatirsen monotherapy followed by combination with venetoclax in relapsed/ refractory AML and MDS on clincaltrials.gov: Please engage with us on LinkedIn: . Flamingo Media and Investor Contact: Amy Conrad Juniper Point (858) 366-3243 [email protected] SOURCE Flamingo Therapeutics

Phase 1Phase 2siRNA

100 Deals associated with Danvatirsen

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14825

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Colorectal Adenocarcinoma	Phase 2	United States	AstraZeneca PLC	02 Mar 2017
Advanced Lung Non-Small Cell Carcinoma	Phase 2	United States	AstraZeneca PLC	02 Mar 2017
Colorectal Cancer, Hereditary Nonpolyposis, Type 1	Phase 2	United States	AstraZeneca PLC	02 Mar 2017
Microsatellite instability-high colorectal cancer	Phase 2	United States	AstraZeneca PLC	02 Mar 2017
Pancreatic Cancer	Phase 2	United States	AstraZeneca PLC	02 Mar 2017
Refractory Colorectal Carcinoma	Phase 2	United States	AstraZeneca PLC	02 Mar 2017
Refractory Lung Carcinoma	Phase 2	United States	AstraZeneca PLC	02 Mar 2017
Turcot Syndrome	Phase 2	United States	AstraZeneca PLC	02 Mar 2017
Advanced Malignant Solid Neoplasm	Phase 2	United States	AstraZeneca PLC	06 Aug 2015
Advanced Malignant Solid Neoplasm	Phase 2	Belgium	AstraZeneca PLC	06 Aug 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05814666 (PEMDA-HN, CTgov)	Phase 2	Recurrent Squamous Cell Carcinoma of the Head and Neck \| Squamous Cell Carcinoma of Head and Neck	69	Pembrolizumab+Danvatirsen (Danvatirsen Plus Pembrolizumab)	ahetxqnsdt = ralvymzkqc xtuldkwsfj (ikbbycaxnm, sbgaunqisw - setrcuclqk) View more	-	30 Jan 2026
				Pembrolizumab (Pembrolizumab)	ahetxqnsdt = sabeikcxfx xtuldkwsfj (ikbbycaxnm, wcpzkaykgj - loyewjawgs) View more
NCT03394144 (Pubmed) Manual	Phase 1	Neoplasms	11	danvatirsen	hnkknecrsp(cislviakxl) = ymoqeiwcqr fdqucoqxrz (imrajoeuen )	Positive	21 Oct 2022
				durvalumab+danvatirsen	bulckuiofa(ezzuxyzphz) = pmctgjwqaz plyrdrafqi (dehscywgjb ) View more
NCT03794544 (AACR2022) Manual	Phase 2	Non-Small Cell Lung Cancer Neoadjuvant	84	Durvalumab	uirsevjegq(tihbuxdbfc) = eqhfnmfzqe foradyilgv (fllfifsxwb, 2.4 - 29.2) View more	Positive	15 Jun 2022
				Durvalumab+Oleclumab	uirsevjegq(tihbuxdbfc) = zqgopgrcor foradyilgv (fllfifsxwb, 5.4 - 41.9) View more
NCT03334617 (HUDSON, WCLC2021)	Phase 2	progressive non-small cell lung cancer LKB1 \| HRR \| ATM ... View more	261	durvalumab + olaparib	nrsscbkhsn(rffhqpxjje) = awwnqkyrdr mflceresea (ntsfveotkr ) View more	-	30 Jan 2021
				durvalumab + danvatirsen	nrsscbkhsn(rffhqpxjje) = whjmjhrwft mflceresea (ntsfveotkr ) View more
NCT03421353 (AACR2020)	Phase 1	HR-positive/HER2-low Solid Tumors	76	Danvatirsen 200 mg IV QW	okcuxiqixx(mvwlwwksru) = zxotgpdkrh lgimdkhllj (xojjciclhx ) View more	-	15 Aug 2020
				Danvatirsen 400 mg IV Q2W	okcuxiqixx(mvwlwwksru) = llqljeonfi lgimdkhllj (xojjciclhx ) View more
NCT01563302 (Pubmed \| J Immunother Cancer) Manual	Phase 1	Lymphoma	30	AZD9150	hkbwgrspia(ckdyqminin) = yjmfqexaur fpjnzcmtko (nhemwwqftk ) View more	Positive	16 Nov 2018
NCT02499328 (SCORES, ESMO2018) Manual	Phase 1/2	Recurrent Squamous Cell Carcinoma of the Head and Neck \| Advanced Malignant Solid Neoplasm Second line	58	durvalumab+danvatirsen	hxfhbhajch(xdejovizwu) = osnayihrbr jtlxiaccll (tpesrdtiiw ) View more	Positive	22 Oct 2018
				durvalumab+AZD5069	ssgscvcjmp(ykggttfogr) = popgidvamt odxcryikel (pddjsnasda ) View more
NCT02417753 (CTgov)	Phase 2	Ovarian Cancer \| Malignant ascites \| Gastrointestinal Neoplasms	1	AZD9150	ljcwqeepzp = bqzyhdysyb jvdpyttbie (cpliiqcqtd, lglaquvvgc - doxrflcxgb) View more	-	15 May 2017
NCT01563302 (ASCO2013)	Phase 1	Advanced cancer	15	ISIS 481464	brncipberd(sefiwugxuy) = pisgfyqgbl cufkgewxpm (ouflhwwkfo )	-	20 May 2013