Delving into the Latest Updates on Andes-1537 with Synapse

Overview

Basic Info

Drug Type

ASO

Synonyms

Mulnitorsen

Target-

Action

stimulants

Mechanism

Apoptosis stimulants, RNA interference

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication-

Inactive Indication

Advanced Malignant Solid NeoplasmColorectal CancerGallbladder Carcinoma+ [3]

Originator Organization

Andes Biotechnologies SA

Active Organization-

Inactive Organization

Andes Biotechnologies SA

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

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Structure/Sequence

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Sequence Code 29706596

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The study is a Phase 1 Open-label Two-stage, Safety and Tolerability Study with Cancer Type-specific Cohorts, Evaluating Subcutaneous Administration of Andes-1537 for Injection in Patients with Advanced Solid Tumors that are Refractory to Standard Therapy or For Which No Standard Therapy Is Available. Patients with unresectable solid tumors that are refractory or have failed standard therapy and are deemed non-eligible or intolerant to further therapy or for which no standard therapy is available will be included in 5 cancer type-specific parallel cohorts. The following tumor types will be evaluated for potential inclusion in each cancer type-specific cohort: gallbladder & biliary tract carcinoma; cervical carcinoma; gastric carcinoma; pancreatic carcinoma, and colorectal carcinoma.

Start Date26 Apr 2019

Sponsor / Collaborator

Andes Biotechnologies SA

NCT02508441

/ TerminatedPhase 1

A Phase 1 Open-label First-in-human Dose-escalating Safety and Tolerability Study Evaluating Subcutaneous Administration of Andes-1537 for Injection in Patients With Advanced Unresectable Solid Tumors That Are Refractory to Standard Therapy or For Which No Standard Therapy is Available

This is a first-in-human, open-label, dose escalation and expansion, 2-part study to determine the safety, tolerability, and maximum tolerated dose of Andes-1537 for Injection in patients with advanced unresectable solid tumors that are refractory to standard therapy or for which no standard therapy is available.

Start Date08 Dec 2015

Sponsor / Collaborator

Andes Biotechnologies SA

100 Clinical Results associated with Andes-1537

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100 Translational Medicine associated with Andes-1537

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100 Patents (Medical) associated with Andes-1537

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2

Literatures (Medical) associated with Andes-1537

06 Sep 2016·Oncotarget

Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors

Article

Author: Valenzuela, Sebastián ; Socias, Miguel ; Briones, Macarena ; Socias, Teresa ; Fitzpatrick, Christopher ; Borgna, Vincenzo ; Echenique, Javiera ; Lopez, Constanza ; Varas, Manuel ; Silva, Verónica ; Lobos-González, Lorena ; Araya, Mariela ; Oliveira-Cruz, Luciana ; Burzio, Verónica A. ; Díaz, Jorge ; Burzio, Luis O. ; Villota, Claudio ; Villegas, Jaime ; Vidaurre, Soledad ; Restovic, Franko

We reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, suggesting this approach for selective therapy against different types of cancer. In order to translate these results to a preclinical scenario, we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display structures similar to the human counterparts, including long double-stranded regions arising from the presence of inverted repeats. Knockdown of ASncmtRNAs with specific antisense oligonucleotides (ASO) reduces murine melanoma B16F10 cell proliferation and induces apoptosis in vitro through downregulation of pro-survival and metastasis markers, particularly survivin. For in vivo studies, subcutaneous B16F10 melanoma tumors in C57BL/6 mice were treated systemically with specific and control antisense oligonucleotides (ASO). For metastasis studies, tumors were resected, followed by systemic administration of ASOs and the presence of metastatic nodules in lungs and liver was assessed. Treatment with specific ASO inhibited tumor growth and metastasis after primary tumor resection. In a metastasis-only assay, mice inoculated intravenously with cells and treated with the same ASO displayed reduced number and size of melanoma nodules in the lungs, compared to controls. Our results suggest that ASncmtRNAs could be potent targets for melanoma therapy. To our knowledge, the ASncmtRNAs are the first potential non-nuclear targets for melanoma therapy.

Scientific ReportsQ3 · CROSS-FIELD

Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells

Q3 · CROSS-FIELD

ArticleOA

Author: Silva, Verónica ; Bustos, Rocío ; Ezquer, Fernando ; Lobos-González, Lorena ; Vera, Tamara ; Varas-Godoy, Manuel ; Burzio, Verónica A ; Silva, Valeria ; Ezquer, Marcelo ; Jeldes, Emanuel ; Villegas, Jaime ; Salomon, Carlos ; Cáceres-Verschae, Albano ; Campos, América ; Duran, Eduardo

AbstractDuring intercellular communication, cells release extracellular vesicles such as exosomes, which contain proteins, ncRNAs and mRNAs that can influence proliferation and/or trigger apoptosis in recipient cells, and have been proposed to play an essential role in promoting invasion of tumor cells and in the preparation of metastatic niches. Our group proposed the antisense non-coding mitochondrial RNA (ASncmtRNA) as a new target for cancer therapy. ASncmtRNA knockdown using an antisense oligonucleotide (ASO-1537S) causes massive death of tumor cells but not normal cells and strongly reduces metastasis in mice. In this work, we report that exosomes derived from ASO-1537S-treated MDA-MB-231 breast cancer cells (Exo-1537S) inhibits tumorigenesis of recipient cells, in contrast to exosomes derived from control-ASO-treated cells (Exo-C) which, in contrast, enhance these properties. Furthermore, an in vivo murine peritoneal carcinomatosis model showed that Exo-1537S injection reduced tumorigenicity compared to controls. Proteomic analysis revealed the presence of Lactadherin and VE-Cadherin in exosomes derived from untreated cells (Exo-WT) and Exo-C but not in Exo-1537S, and the latter displayed enrichment of proteasomal subunits. These results suggest a role for these proteins in modulation of tumorigenic properties of exosome-recipient cells. Our results shed light on the mechanisms through which ASncmtRNA knockdown affects the preparation of breast cancer metastatic niches in a peritoneal carcinomatosis model.

100 Deals associated with Andes-1537

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Colorectal Cancer	Phase 1	Chile	Andes Biotechnologies SA	26 Apr 2019
Gallbladder Carcinoma	Phase 1	Chile	Andes Biotechnologies SA	26 Apr 2019
Pancreatic Cancer	Phase 1	Chile	Andes Biotechnologies SA	26 Apr 2019
Stomach Cancer	Phase 1	Chile	Andes Biotechnologies SA	26 Apr 2019
Uterine Cervical Cancer	Phase 1	Chile	Andes Biotechnologies SA	26 Apr 2019
Advanced Malignant Solid Neoplasm	Phase 1	United States	Andes Biotechnologies SA	08 Dec 2015
Advanced Malignant Solid Neoplasm	Phase 1	United States	Andes Biotechnologies SA	08 Dec 2015

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02508441 (ASCO2018)	Phase 1	HR-positive/HER2-low Solid Tumors	22	Andes-1537	(wpxxpgbhwg) = Two dose-limiting toxicities occurred at the 800 mg dose level both of which were injection site reactions: one precluding full cycle 1 dose delivery, and one involving grade 3 skin necrosis due to vascular occlusion and inflammation. fcolhcylvo (kwarvncszz ) View more	Positive	01 Jun 2018