Delving into the Latest Updates on Atu-027 with Synapse

Overview

Basic Info

Drug Type

siRNA

Synonyms

AtuRNAi silencing PKN3 + AtuPlex

Target

PKN3

Action

inhibitors

Mechanism

PKN3 inhibitors(Serine/threonine-protein kinase N3 inhibitors), RNA interference

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmPancreatic adenocarcinoma metastaticPancreatic Ductal Carcinoma

Originator Organization

Silence Therapeutics Plc

Active Organization-

Inactive Organization

Silence Therapeutics GmbH

License Organization-

Drug Highest PhasePendingPhase 1/2

First Approval Date-

Regulation-

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Structure/Sequence

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Sequence Code 29511790

Source: *****

Sequence Code 30104753

Source: *****

The purpose of the study is to evaluate a new treatment strategy for advanced pancreatic cancer disease by combining the new investigational medicinal product Atu027 with the standard chemotherapeutic gemcitabine. This combination aims at enhancing gemcitabine´s anti-tumor activity with Atu027.
The objectives of this clinical trial are to evaluate safety and activity of two Atu027 schedules in combination with standard gemcitabine treatment in patients with advanced or metastatic pancreatic adenocarcinoma.

Start Date01 Mar 2013

Sponsor / Collaborator

Silence Therapeutics GmbH

[+2]

NCT00938574

/ CompletedPhase 1

A Prospective, Open-label, Single Center, Dose Finding Phase I-study With Atu027 (an siRNA Formulation) in Subjects With Advanced Solid Cancer

This is a phase I, prospective, open-label, single center, dose finding study with Atu027 (an siRNA formulation) given as single treatment followed by repeated treatment (repeated treatment phase: 8 treatments within 4 weeks) as therapy in subjects with advanced solid cancer.

Start Date01 Jun 2009

Sponsor / Collaborator

Silence Therapeutics GmbH

100 Clinical Results associated with Atu-027

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100 Translational Medicine associated with Atu-027

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100 Patents (Medical) associated with Atu-027

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8

Literatures (Medical) associated with Atu-027

01 Mar 2018·Pharmaceutical Research

Correction to: The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market

Author: Titze-de-Almeida, Ricardo ; David, Catherine ; Titze-de-Almeida, Simoneide Souza

The published article contains an error in Figure 5. The term "Atu027" should be substituted by "Patisiran" in figure and legend.

01 Jul 2017·Pharmaceutical ResearchQ3 · MEDICINE

The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market

Q3 · MEDICINE

Review

Author: Titze-de-Almeida, Ricardo ; David, Catherine ; Titze-de-Almeida, Simoneide Souza

Ten years after Fire and Melo's Nobel Prize for discovery of gene silencing by double-stranded RNA, a remarkable progress was achieved in RNA interference (RNAi). Changes in the chemical structure of synthetic oligonucleotides make them more stable and specific, and new delivery strategies became progressively available. The attention of pharmaceutical industry rapidly turned to RNAi, as an opportunity to explore new drug targets. This review addresses nine small-interfering RNAs (siRNAs) and one unique microRNA (miRNA) inhibitor, which entered the phase 2-3 clinical trials. The siRNAs in focus are PF-04523655, TKM-080301, Atu027, SYL040012, SYL1001, siG12D-LODER (phase 2), QPI-1002, QPI-1007, and patisiran (phase 3). Regarding miRNAs, their content can be down- or up-regulated, by using miRNA inhibitors (AntimiRs) or miRNA mimics. Miravirsen is an AntimiR-122 for hepatitis C virus infection. The flexibility of RNAi technology is easily understood taking into account: (i) the different drug targets (i.e. p53, caspase 2, PKN3, β2-adrenergic receptor, mutated KRAS, microRNAs); (ii) therapeutic conditions, including ophthalmic diseases, kidney injury, amyloidosis, pancreatic cancer, viral hepatitis; and (iii) routes of administration (ocular, intravenous, subcutaneous, intratumoral). Although some issues are still matters of concern (delivery, toxicity, cost, and biological barriers), RNAi definitively opens a wide avenue for drug development.

20 Dec 2014·Journal of Clinical OncologyQ1 · MEDICINE

First-in-Human Phase I Study of the Liposomal RNA Interference Therapeutic Atu027 in Patients With Advanced Solid Tumors

Q1 · MEDICINE

Article

Author: Lange, Christian ; Giese, Klaus ; Drevs, Joachim ; Strumberg, Dirk ; Gebhardt, Frank ; Vank, Christiane ; Khan, Michael ; Schultheis, Beate ; Kaufmann, Jörg ; Santel, Ansgar ; Keil, Oliver

Purpose Atu027 is a novel liposomal RNA interference therapeutic that includes a short-interfering RNA (siRNA), which silences expression of protein kinase N3 in the vascular endothelium. Atu027 has previously been shown to inhibit local tumor invasion as well as lymph node and pulmonary metastasis in mouse cancer models. This first-in-human study aimed to assess the safety, tolerability, and pharmacokinetics of Atu027 while evaluating therapeutic effects on both primary tumors and metastatic lesions. Patients and Methods Thirty-four patients with advanced solid tumors received 10 escalating doses of Atu027 without premedication, as one single followed by eight intravenous infusions twice per week during a 28-day cycle. Response was monitored by computed tomography/magnetic resonance imaging at baseline, at the end of treatment (EoT), and at final follow-up (EoS), and was assessed according to RECIST. Results Atu027 was well tolerated up to dose levels of 0.336 mg/kg; most adverse events (AEs) were low-grade toxicities (grade 1 or 2). No maximum tolerated dose was reached. Plasma levels of siRNA strands and lipids were dose proportional, peaking during 4-hour infusion. Disease stabilization was achieved in 41% of patients at EoT (n = 14 of 34 treated patients); eight patients had stable disease at EoS, and some experienced complete or partial regression of metastases. sFLT1 (soluble variant of vascular endothelial growth factor receptor-1) decreased from pretreatment levels in most patients after dose levels 04 to 10. Conclusion Atu027 was safe in patients with advanced solid tumors, with 41% of patients having stable disease for at least 8 weeks. In view of these results, further clinical trials have been initiated, and sFLT1 will be investigated as a potential biomarker.

100 Deals associated with Atu-027

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12171

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic adenocarcinoma metastatic	Phase 2	Germany	Silence Therapeutics GmbH	01 Mar 2013
Pancreatic Ductal Carcinoma	Phase 2	Germany	Silence Therapeutics GmbH	01 Mar 2013
Advanced Malignant Solid Neoplasm	Phase 2	Germany	Silence Therapeutics GmbH	01 Jun 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01808638 (Atu027-I-02, Pubmed \| Cancers (Basel))	Phase 1/2	Pancreatic adenocarcinoma	23	Gemcitabine + Atu027 (0.235 mg/kg once weekly)	(ipdcmtmeua) = wmudyuotdu cjzazpeleq (oitocecusd )	Positive	26 Oct 2020
NCT01808638 (Atu027-I-02, Pubmed \| Cancers (Basel))	Phase 1/2	Pancreatic adenocarcinoma	23	Gemcitabine + Atu027 (0.235 mg/kg twice weekly)	(ipdcmtmeua) = mnqhekcqli cjzazpeleq (oitocecusd )	Positive	26 Oct 2020
NCT01808638 (Atu027-I-02, ASCO_GI2016) Manual	Phase 1/2	Pancreatic adenocarcinoma	23	gemcitabine+Atu027 0.253mg/kg once weekly	(xdbavoptuv) = cpzrqvefvd ffjbxawske (felteewxdq, 0.4 - 5.5) View more	Positive	01 Feb 2016
NCT01808638 (Atu027-I-02, ASCO_GI2016) Manual	Phase 1/2	Pancreatic adenocarcinoma	23	gemcitabine+Atu027 0.253mg/kg twice-weekly	(xdbavoptuv) = qsbyzjvbda ffjbxawske (felteewxdq, 1.5 - 6.0) View more	Positive	01 Feb 2016
NCT00938574 (Pubmed \| J Clin Oncol)	Phase 1	Advanced Malignant Solid Neoplasm sFLT1	34	Atu027	uygwiyltgg(robifdiibf) = ddpmqwcwcf rssdoezodc (czkvdxeicm )	Positive	20 Dec 2014
NCT00938574 (ASCO2013)	Phase 1	Advanced cancer	34	Atu027	qvxiafjzvy(wlrnxiaddt) = nhtlcwgehq mocvxtjnqy (xihoeosdzy )	Positive	20 May 2013
ASCO2012	Phase 1	Advanced Malignant Solid Neoplasm	33	Atu027	mdzkhkpjer(kwobqdmchr) = scqfejqwke bkksdavxxe (bfupycoeob ) View more	Positive	20 May 2012
ASCO2011	Phase 1	Advanced Malignant Solid Neoplasm	21	Atu027	(jsjtkphvko) = eygfdnekva zcmkyxghaq (grqmnychnn ) View more	Positive	20 May 2011