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

Mechanism

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

Therapeutic Areas

NeoplasmsNervous System DiseasesCongenital Disorders+ [5]

Active Indication

Squamous Cell Carcinoma of Head and NeckAdvanced Colorectal AdenocarcinomaAdvanced Lung Non-Small Cell Carcinoma+ [11]

Inactive Indication

Advanced cancerAdvanced Hepatocellular CarcinomaDiffuse Large B-Cell Lymphoma+ [2]

Originator Organization

Ionis Pharmaceuticals, Inc.

Active Organization

Flamingo Therapeutics BVStartup

AstraZeneca PLC

Dynacure SAStartup

Inactive Organization

MedImmune LLC

Ionis Pharmaceuticals, Inc.

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 BVStartup

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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19

Literatures (Medical) associated with Danvatirsen

01 Mar 2024·Nature MedicineQ1 · MEDICINE

Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial

Q1 · MEDICINE

Article

Author: Hartl, Sylvia ; Awad, Mark M ; Vicente, David ; Russell, Deanna L ; Moskovitz, Mor T ; Pons-Tostivint, Elvire ; Hobson, Rosalind ; Cousin, Sophie ; Johnson, Melissa L ; Hochmair, Maximilian J ; Conway, James P ; Thomas, Michael ; Barry, Simon T ; Florescu, Marie ; Heymach, John V ; Iyer, Sonia ; Dressman, Marlene ; Forde, Patrick M ; Shepherd, Frances A ; Chu, Quincy S C ; Kumar, Rakesh ; Dean, Emma ; Kim, Sang-We ; Park, Keunchil ; Khosla, Sajan ; Cosaert, Jan ; Morgensztern, Daniel ; Cheema, Parneet ; Keddar, Mohamed Reda ; Wheatley-Price, Paul ; Ambrose, Helen J ; Reddy, Avinash ; Goss, Glenwood ; Aronson, Boaz ; Jewsbury, Philip J ; Barrett, J Carl ; Besse, Benjamin ; Kim, Dong-Wan

AbstractFor patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance—which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment—and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of anti-PD-(L)1-containing immunotherapy and platinum-doublet therapy. A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)–ceralasertib (ATR kinase inhibitor), durvalumab–olaparib (PARP inhibitor), durvalumab–danvatirsen (STAT3 antisense oligonucleotide) or durvalumab–oleclumab (anti-CD73 monoclonal antibody). Greatest clinical benefit was observed with durvalumab–ceralasertib; objective response rate (primary outcome) was 13.9% (11/79) versus 2.6% (5/189) with other regimens, pooled, median progression-free survival (secondary outcome) was 5.8 (80% confidence interval 4.6–7.4) versus 2.7 (1.8–2.8) months, and median overall survival (secondary outcome) was 17.4 (14.1–20.3) versus 9.4 (7.5–10.6) months. Benefit with durvalumab–ceralasertib was consistent across known immunotherapy-refractory subgroups. In ATM-altered patients hypothesized to harbor vulnerability to ATR inhibition, objective response rate was 26.1% (6/23) and median progression-free survival/median overall survival were 8.4/22.8 months. Durvalumab–ceralasertib safety/tolerability profile was manageable. Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab–ceralasertib is under further investigation in immunotherapy-refractory NSCLC.ClinicalTrials.gov identifier: NCT03334617

01 Nov 2023·Cancer Discovery

Neoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial

Article

Author: García-Campelo, Rosario ; Hussein, Maen ; Hamid, Oday ; Anagnostou, Valsamo ; Tan, Tze Heng ; Cascone, Tina ; Gopalakrishnan, Vancheswaran ; Soo-Hoo, Yee ; Mazieres, Julien ; Spigel, David R ; Rodriguez-Canales, Jaime ; McGrath, Lara ; Forde, Patrick M ; Oliveira, Julio ; Grenga, Italia ; Sellman, Bret R ; Spira, Alexander I ; Zheng, Ying ; Kar, Gozde ; Kumar, Rakesh ; Blando, Jorge ; Spicer, Jonathan D ; Cheng, Lin-Yang ; Yau, Edwin H ; Surace, Michael ; Weder, Walter ; Mager, Raymond ; Daniel, Davey B

AbstractNeoadjuvant chemoimmunotherapy improves pathologic complete response rate and event-free survival in patients with resectable non–small cell lung cancer (NSCLC) versus chemotherapy alone. NeoCOAST was the first randomized, multidrug platform trial to examine novel neoadjuvant immuno-oncology combinations for patients with resectable NSCLC, using major pathologic response (MPR) rate as the primary endpoint. Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti–PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). MPR rates were higher for patients in the combination arms versus durvalumab alone. Safety profiles for the combinations were similar to those of durvalumab alone. Multiplatform immune profiling suggested that improved MPR rates in the durvalumab plus oleclumab and durvalumab plus monalizumab arms were associated with enhanced effector immune infiltration of tumors, interferon responses and markers of tertiary lymphoid structure formation, and systemic functional immune cell activation.Significance:A neoadjuvant platform trial can rapidly generate clinical and translational data using candidate surrogate endpoints like MPR. In NeoCOAST, patients with resectable NSCLC had improved MPR rates after durvalumab plus oleclumab or monalizumab versus durvalumab alone and tumoral transcriptomic signatures indicative of augmented immune cell activation and function.See related commentary by Cooper and Yu, p. 2306.This article is featured in Selected Articles from This Issue, p. 2293

01 Sep 2023·Journal of pharmaceutical sciences

Advances in the Specificity of Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy Based Structural Characterisation Methods for Synthetic Oligonucleotides

Article

Author: Whittaker, David T. E. ; Xu, Jingshu ; Benstead, David ; Dias, David M. ; Ray, Andrew ; Coombes, Steven R.

Identity testing is a critical part in the development of a therapeutic synthetic oligonucleotide. Tandem Mass Spectrometry (MS/MS) is commonly used for the analysis of oligonucleotides to obtain structural and sequence information, however there are challenges resulting from chemical modifications introduced to improve their pharmacokinetics and stability. For these structurally complex oligonucleotides, Nuclear Magnetic Resonance (NMR) Spectroscopy has found limited use for characterisation and identity testing, as only partial NMR resonance assignment for oligonucleotides is achieved without isotopic labelling methodologies. Regardless of the choice of method used for oligonucleotide analysis, the specificity is of critical importance. In this work, in-source dissociation mass spectrometry and proton (¹H) and carbon (¹³C) NMR at high temperature were used to analyse danvatirsen, a 16 nucleotide phosphorothioate antisense oligonucleotide, and its closely related switch sequences. Both approaches have shown specificity to distinguish danvatirsen from these similar sequences.

21

News (Medical) associated with Danvatirsen

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

10 Jun 2024

·www.prnewswire.com

Flamingo Therapeutics Announces Poster Presentation at EACR 2024 Congress on FLM-7523 (FTX-001), a First-in-Class Inhibitor of the Long Non-Coding RNA MALAT1

LEUVEN, Belgium and STRASBOURG, France and PHILADELPHIA , June 10, 2024 /PRNewswire/ -- Flamingo Therapeutics ("Flamingo") today announced a poster presentation on FLM-7523 (also referred to as FTX-001) at the Annual Congress of the European Association for Cancer Research (EACR) 2024 Congress, being held in Rotterdam, Netherlands from June 10-13, 2024. Flamingo will present preclinical results highlighting the candidate selection and characterization of FLM-7523, a novel oligonucleotide targeting MALAT1 for the treatment of cancer. Flamingo has advanced FLM-7523 through Phase 1 enabling preclinical activities and is planning for a First-in-Human trial in solid tumors. EACR poster details are as follows: Abstract#: EACR2024-0240 Title: "Preclinical development of FTX-001: First-in-class inhibitor of the long non-coding RNA MALAT1" Session Title: Posters: Experimental/Molecular Therapeutics, Pharmacogenomics Session Date and Time: June 11, 2024, from 11:00 to 20:15 Presenting Author: Dr. Marie-Aline Neveu Abstracts related to the EACR meeting will be published online in a supplement to the FEBS journal, Molecular Oncology, the Congress App and the Congress Website. For more information, please visit the EACR 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

Phase 1Phase 2AACROligonucleotide

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 cancer	Phase 3	US	AstraZeneca PLC	27 Feb 2012
Squamous cell carcinoma of head and neck metastatic	Phase 2	IT	AstraZeneca PLC	06 Aug 2015
Squamous cell carcinoma of head and neck metastatic	Phase 2	BE	AstraZeneca PLC	06 Aug 2015
Squamous cell carcinoma of head and neck metastatic	Phase 2	ES	AstraZeneca PLC	06 Aug 2015
Squamous cell carcinoma of head and neck metastatic	Phase 2	DE	AstraZeneca PLC	06 Aug 2015
Squamous cell carcinoma of head and neck metastatic	Phase 2	US	AstraZeneca PLC	06 Aug 2015
Squamous cell carcinoma of head and neck metastatic	Phase 2	GB	AstraZeneca PLC	06 Aug 2015
Advanced cancer	Discovery	US	Ionis Pharmaceuticals, Inc.	27 Feb 2012
Diffuse Large B-Cell Lymphoma	Discovery	US	AstraZeneca PLC	27 Feb 2012
Diffuse Large B-Cell Lymphoma	Discovery	US	Ionis Pharmaceuticals, Inc.	27 Feb 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03334617 (HUDSON, Pubmed) Manual	Phase 2	Advanced Lung Non-Small Cell Carcinoma	268	Durvalumab-ceralasertib	(vpiwoqqzyk) = eiswxyldqr icemfazzfk (zgwpqlhdlg ) View more	Positive	01 Mar 2024
				Durvalumab-olaparibdanvatirsenoleclumab	(vpiwoqqzyk) = ztirpqgtdc icemfazzfk (zgwpqlhdlg ) View more
NCT03794544 (NeoCOAST, ESMO2022)	Phase 2	Non-Small Cell Lung Cancer Neoadjuvant	84	Durvalumab	(eopnaldtta) = bumzfnthwz arlilmumrg (grirvhhldl )	-	12 Sep 2022
				Durvalumab + Oleclumab	(eopnaldtta) = onddhirrzq arlilmumrg (grirvhhldl )
NCT03794544 (AACR2022) Manual	Phase 2	Non-Small Cell Lung Cancer Neoadjuvant	84	Durvalumab	(psjkvujnng) = uqhrsxpgiv tkphgftubf (wzpymayivc, 2.4 - 29.2) View more	Positive	15 Jun 2022
				Durvalumab+Oleclumab	(psjkvujnng) = reflpnazbc tkphgftubf (wzpymayivc, 5.4 - 41.9) View more
NCT03794544 (NeoCOAST, CTgov)	Phase 2	Non-small cell lung cancer stage IIIA	84	Durvalumab (Durvalumab 1500 mg)	pqmmkmtaus(fploospsol) = kummhxfwzy nwsfggtwtq (yhnwmtfbct, bksqobqiod - ckmssyhxlg) View more	-	24 Feb 2022
				Durvalumab+Oleclumab (Durvalumab 1500 mg + Oleclumab 3000 mg)	pqmmkmtaus(fploospsol) = njknmslrwq nwsfggtwtq (yhnwmtfbct, icofxjjzba - oeanxnhrpe) View more
NCT03421353 (AACR2020)	Phase 1	HR-positive/HER2-low Solid Tumors	76	Danvatirsen 200 mg IV QW	ulxizcsbeg(qpthkriimh) = utzksvndmm kftgdvbdko (zsvgthjzwt ) View more	-	15 Aug 2020
				Danvatirsen 400 mg IV Q2W	ulxizcsbeg(qpthkriimh) = vktfltyloa kftgdvbdko (zsvgthjzwt ) View more
NCT01563302 (Pubmed \| J Immunother Cancer) Manual	Phase 1	Lymphoma	30	AZD9150	(lsjsrjqypw) = xbbepucgja wacbxmzrrw (dqyehesiyc ) 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	(lmwyembind) = nwyhedpshb ieopbrdfml (sxatymjeoy ) View more	Positive	22 Oct 2018
				durvalumab+AZD5069	(kcirapzukz) = nvhoulqrzo yihoweoyee (bnqgbbymeg ) View more
NCT02417753 (CTgov)	Phase 2	Ovarian Cancer \| Malignant ascites \| Gastrointestinal Neoplasms	1	AZD9150	cxodtlwihr(vehzgbyjrg) = obbzmjhqqu pzzfdkpvwa (emuvizvkth, wpuzsbzibf - swfxxlpkqn) View more	-	15 May 2017
NCT01563302 (ASCO2013)	Phase 1	Advanced cancer	15	ISIS 481464	(ywgqdpnfso) = vbebgdqrwc hdapfdpept (dsvzajyhrc )	-	20 May 2013