Publications & Grants

The latest publications and competitive R&D grants related to our research work, on advanced RNA treatments against genetic diseases,can be consulted online on this page.

Design of the first in human ArthemiR™ study of a novel drug, ATX-01, for the treatment of DM1
ATX-01 is a novel anti-microRNA in clinical development for the treatment of Myotonic Dystrophy. The objective of the current project was to design an efficient and feasible study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical efficacy of ascending single and multiple doses of ATX-01 in participants with adult-onset Myotonic Dystrophy Type 1 (DM1).
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Fatty Acid Mediated Uptake System enables improved oligo delivery to muscle and brain
Oligonucleotide-therapeutics represent an emerging drug discovery platform designed to modulate gene expression targeting DNA or RNA in a sequence specific manner. The development of these molecules involves improved chemistry and conjugates to overcome extracellular and intracellular obstacles and efficiently reach their targets. However, delivery to skeletal muscle and central nervous system (CNS) remains a challenge. To enhance biodistribution, efficacy, and safety in a clinically acceptable manner, we investigated the effects on efficacy and biodistribution of applying Arthex’s scaffold (oleic acid conjugation plus link to a defined chemical modification pattern in the oligo) to an antimiR-23b as a potentital therapy for Myotonic Dystrophy type 1 (DM1). The lead molecule X82108 was tested in the experiments detailed below and is now being tested in a human clinical trial as drug product ATX-01, in the ArthemiR trial of adults with DM1
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New insights into DM1 mechanism of pathogenesis: DMPK, MBNL and miR-23b balance as the master key of DM1 pathology
Myotonic dystrophy type 1 (DM1) is a severe genetic disorder caused by the expansion of CTG repeats in the DMPK gene. This expansion results in the accumulation of toxic RNA in ribonuclear foci, which sequester the splicing regulator muscleblind-like (MBNL) protein, leading to spliceopathy. In addition to sequestration, recent findings have confirmed that downregulation of MBNL proteins is sufficient to produce symptoms of DM1. ATX-01 is a novel oligonucleotide-based therapy currently in clinical development for DM1. It directly inhibits miR-23b, a negative regulator of MBNL1 translation. Notably, ATX-01 treatment has been associated with reduced ribonuclear foci and lower DMPK mRNA levels in in vitro and in vivo DM1 models. This study aims to provide a broader understanding of DM1 pathogenesis by investigating how miR-23b downregulation contributes to the reduction of mutant DMPK transcripts.
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Fatty Acid Mediated Oligonucleotide Uptake System enables antimiR-23b mediated functional and molecular rescue of cognitive dysfunction in DMSXL mice
Myotonic dystrophy type 1 (DM1) is a rare genetic disease with severe neuromuscular symptoms, and it is the most common form of muscular dystrophy. The congenital manifestation, CDM, is particularly aggressive, affecting not only muscles but also various organs, including the brain. Cognitive deficits, anhedonia, daytime sleepiness, loss of memory, and intellectual disabilities are observed in CDM due to brain alterations. The genetic origin of both diseases is the abnormal expansion of CTG repeats in the 3´UTR of DMPK gene. This expansion results in the accumulation of toxic mRNA in nuclear foci, sequestering critical proteins for RNA splicing regulation such as MBNL1/2. CDM is characterized by a higher number of CTG repeats in the DMPK gene, which leads to reduced levels of functional (not-sequestered) MBNL proteins. Previous studies have identified a link between miR-23b and DM1 pathogenesis, and have shown the therapeutic potential of reducing miR-23b activity in in vivo DM1 models of muscular phenotype. This work aims to demonstrate that an oleic acid–conjugated antimiR-23b (X82108) can efficiently rescue brain-related DM1 phenotypes after systemic administration in DMSXL mice, which carry over 1000 CTG repeats with central nervous system (CNS) expression, in preparation for clinical trials in CDM1 and Chilhood DM (ChDM) patients. X82108 is the active pharmaceutical ingredient in ATX-01 currently in a Phase I/II clinical trial in participants with Adult DM1.
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A two-pronged approach to myotonic dystrophy type 1
Spain’s ARTHEx Biotech has developed a dual-mechanism approach to treating the most common adult-onset muscular dystrophy, myotonic dystrophy type 1, setting it apart in a burgeoning blockbuster market.
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AntimiR treatment corrects myotonic dystrophy primary cell defects across several CTG repeat expansions with a dual mechanism of action
This study evaluated therapeutic antimiRs in primary myoblasts from patients with myotonic dystrophy type 1 (DM1). DM1 results from unstable CTG repeat expansions in the DMPK gene, leading to variable clinical manifesta- tions by depleting muscleblind-like splicing regulator protein MBNL1.
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New ARTHEx Biotech presentation at the 2022 Myotonic Dystrophy Foundation program "Meet the DM drug developers"
Meet the DM drug developers is a program organized by the Myotonic Dystrophy Foundation where each month biotechnology, pharmaceutical and academic partners, large and small, working on treatments for myotonic dystrophy sit down with the Myotonic Dystrophy Foundations community to share their progress and answer their questions. Watch Arthex's presentation on June 10, 2022, where we explain our updated program for the development of ATX-01.
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Lead antimiR-23b drug rescues cell phenotypes in a range of myotonic dystrophy genetic backgrounds
Judy Walker, Estefanía Cerro-Herreros, Judit Núñez-Manchón, Neia Naldaiz-Gastesi, Marc Carrascosa, Sàez, Andrea García-Rey, Irene González-Martínez, Kevin Moreno, Javier Poyatos-García, Juan J Vilchez, Adolfo López de Munain, Mònica Suelves, Gisela Nogales-Gadea, Beatriz Llamusí and Rubén Artero. 2022 MDF Annual Conference. 9th-10th September. San Diego (California)
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Proof of concept of peptide-linked blockmiR-induced MBNL functional rescue in myotonic dystrophy type 1 mouse model
Sarah J. Overby, Estefanía Cerro-Herreros, Irene González-Martínez, Miguel A. Varela, David Seoane-Miraz, Yahya Jad, Richard Raz, Thorleif Møller, Manuel Pérez-Alonso, Matthew J. Wood, Beatriz Llamusí, Rubén Artero. Proof of concept of peptide-linked blockmiR-induced MBNL functional rescue in myotonic dystrophy type 1 mouse model. Molecular Therapy - Nucleic Acids, Volume 27,2022, Pages 1146-1155.
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ARTHEx biotech presentation at the Myotonic Dystrophy Foundation program "Meet the DM drug developers"
Meet the DM drug developers is a program organized by the Myotonic Dystrophy Foundation where each month biotechnology, pharmaceutical and academic partners, large and small, working on treatments and a cure for myotonic dystrophy sit down with the Myotonic Dystrophy Foundations community to share their progress and answer their questions. Watch Arthex's presentation on June 9, 2021, where we explain our program for the development of ATX-01.
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miR-23b and miR-218 silencing increase Muscleblind-like expression and alleviate myotonic dystrophy phenotypes in mammalian models
Estefania Cerro-Herreros, Maria Sabater-Arcis, Juan M. Fernandez-Costa, Nerea Moreno, Manuel Perez-Alonso, Beatriz Llamusi, Ruben Artero Nat Commun. 2018; 9: 2482.
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Preclinical characterization of antagomiR-218 as a potential treatment for myotonic dystrophy
Estefanía Cerro-Herreros, Irene González-Martínez, Nerea Moreno, Jorge Espinosa-Espinosa, Juan M. Fernández-Costa, Anna Colom-Rodrigo, Sarah J. Overby, David Seoane-Miraz, Javier Poyatos-García, Juan J. Vilchez, Adolfo López de Munain, Miguel A. Varela, Matthew J. Wood, Manuel Pérez-Alonso, Beatriz Llamusí, Rubén Artero Mol Ther Nucleic Acids. 2021 Dec 3; 26: 174–191.
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Therapeutic Potential of AntagomiR-23b for Treating Myotonic Dystrophy
Estefanía Cerro-Herreros, Irene González-Martínez, Nerea Moreno-Cervera, Sarah Overby, Manuel Pérez-Alonso, Beatriz Llamusí, Rubén Artero Mol Ther Nucleic Acids. 2020 Sep 4; 21: 837–849.
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Instituto Valenciano de Competitividad Empresarial (IVACE). PROYECTOS DE I+D DE PYME (PIDI-CV)

ARTHEx has been awarded funding by GVA-IVACE to support R&D and innovation projects. The approved project, titled "Development of Novel Delivery Systems for Therapeutic Oligonucleotides Targeting Specific Tissues" (“Desarrollo de nuevos sistemas de liberación de oligonucleótidos terapéuticos dirigidos a tejidos diana”) (IMIDTA/2024/22), aims to advance cutting-edge technologies for the precise delivery of oligonucleotide-based therapeutics.

This initiative is part of the R&D Projects for SMEs (PIDI-CV) 2024 program and is co-financed by the European Union through the European Regional Development Fund (Fondos FEDER). The total eligible cost of the project is 169.910 €, of which 70.682,56 € has been granted as a subsidy.

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Proyectos en Colaboración Público Privada 2022

The project “Translational Research on Myotonic Dystrophy for the Development of an RNA Based Advanced Therapy (DISMIOTATX)” with reference CPP2022-009960 is granted by the “Proyectos en Colaboración Público Privada 2022” program funded by MCIN/AEI/10.13039/501100011033 and, as appropriate by the “European Union NextGenerationEU/PRTR”.

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AVI INNTAL L2

ARTHEx receives financial support from the Talent Promotion Program-Line 2 of GVA-AVI for the execution of the project "Development of the pivotal (GLP) and toxicity studies program for an RNA drug" (INNTA2/2023/10). The project is granted with 75.184,18€, with co-financing from the European Union through the European Regional Development Fund (FEDER) 2021-2027.

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AVI INNTAL L3

The project funded by the grant INNTA3/2023/16 of the Talent Promotion Program-Line 3 of GVA-AVI with co-financing from the European Union through the European Regional Development Fund (FEDER) 2021-2027, has explored new therapeutic strategies for myotonic dystrophy type 2 (DM2) and Fuchs' endothelial corneal dystrophy (FECD), two unmet medical diseases caused by splicing alterations. The project has evaluated the efficacy of an experimental antimiR to modulate the expression of microRNAs involved in these pathologies, using in vivo and in vitro models.

The results have included the characterization of an in vivo model of FECD and a proof of concept with an experimental antimiR in animal and cellular models.Additionally, cellular models of DM2 have been established to study splicing alterations.

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Conselleria de Economía Sostenible, Sectores Productivos, Comercio y Trabajo

Arthex has been a beneficiary of a grant to support the external promotion of the Comunitat Valenciana in the framework of the covid-19 crisis, for the 2022 fiscal year from the Conselleria de Economía Sostenible, Sectores Productivos, Comercio y Trabajo (grant reference INTPRM/2022/764).

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Proyectos I+D+i en «Líneas Estratégicas» 2022

The project “New fly and 3D cell tools for the development of therapeutic oligonucleotides” with reference PLEC2022-009367 is granted by the “Proyectos I+D+i en «Líneas Estratégicas” program funded by MCIN/AEI/10.13039/501100011033 and, as appropriate by the “European Union NextGenerationEU/PRTR”.

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Proyectos en Colaboración Público Privada 2021

The project “Development of a first-in-class therapy for the treatment of osteoarthritis (OA) based on microRNA inhibitor oligonucleotides” with reference CPP2021-008792 is granted by the “Proyectos en Colaboración Público Privada 2021” program funded by MCIN/AEI/10.13039/501100011033 and, as appropriate by the “European Union NextGenerationEU/PRTR”.

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FIGHT-DM1

This project has been co-funded by the European Union`s EIC Accelerator program with a 2.5M€ grant, under the Grant Agreement Nº 190181217.

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Innovative SME
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Arthex Biotech is granted as Innovative SME by the Spanish Ministry of Science and Innovation in compliance with the national legislation (Orden ECC/1087/2015, de 5 de junio).
Generalitat Valenciana - Institut Valencià de Finances

ARTHEx has benefited from a financial instrument within the Operational Program of the European Regional Development Fund (FEDER) of the Valencian Community 2014-2020("Venture Capital to Support Business Growth"), managed by the Valencian Institute of Finance (IVF), in collaboration with In Vivo Capital Partners SGEIC, S.A., to support businesses in the Valencian Community with high growth potential.

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CDTI Misiones

ARTHEx is participating in the "OLIGOFASTX: Comprehensive Platform for the Sustainable Development of Oligonucleotide-Based Therapies" project. The general objective of this project is to develop a comprehensive platform for new therapies based on oligonucleotides (AntimiRNAs, siRNAs, and aptamers) that promotes and facilitates the market introduction of new therapies for rare diseases without medical solutions. This project is subsidized by CDTI with the support of the Ministry of Science and Innovation and the European Union's Recovery, Transformation, and Resilience Plan (financed by the European Union-Next Generation EU). The total eligible cost for ARTHEx is €873,439.20. In addition to ARTHEx, the following entities are participating in this project: Sylentis, S.A.U; AptaTargets, S.L.; Aptus Biotech, S.L.; Nostrum Biodiscovery, S.L.; Nanovex Biotechnologies, S.L.; and Biotechnology Development for Industry in Pharmaceutical S.L.U. For more information about the project, please visit:

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Torres Quevedo

ARTHEx is the beneficiary of the Torres Quevedo grant from the “Agencia Estatal de Invetsigación” for the hiring of research personnel. The total eligible cost is €92,489.61. Grant PTQ2020-011110 funded by MCIN/AEI/ 10.13039/501100011033 by“European Union NextGenerationEU/PRTR”.

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IVACE I+D (Valencian Regional Government)

ARTHEx has been granted funding by GVA-IVACE for R&D and innovation projects to carry out the project "In Vitro Efficacy of Oligonucleotides in Different Experimental Disease Models" (IMIDTA/2021/65). The objective of this project is to research the potential of unique antisense RNA oligonucleotides,exclusively developed by the company, as therapeutic targets for various diseases. The total eligible cost is €77,668.81, funded from the 2021 budget,with co-financing from the European Union through the European Regional Development Fund (FEDER).

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AVI INNTAL (Valencian Regional Government)

ARTHEx benefits from the financial support of the Talent Promotion Program - Line 2 of GVA-AVI (Valencian Innovation Agency) for the execution of the project "Development of the CMC program for ATX-01 up to Phase II" (INNTA2/2021/18). The overall objective of the project is to develop the chemistry, manufacturing, and quality program of Arthex Biotech SL necessary to advance our first lead to Phase II clinical trials. The total eligible cost is €173,075.33, funded from the 2021 budget, with co-financing from the European Union through the European Regional Development Fund (FEDER).

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CDTI Neotec

ARTHEx has received support from the Spanish Center for Industrial Technological Development (CDTI) for new business projects of innovative companies (NEOTEC Program), under the State Program for Business R&D and Innovation within the framework of the State Plan for Scientific and Technical Research and Innovation 2017-2020, for the implementation of the project "Antisense Therapy and New Therapeutic Targets for the Treatment of Diseases with Loss of Function of Proteins MBNL1/2" (SNEO-20201136). The total eligible cost is €250,000.

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EIT Health HEADSTART

ARTHEx is supported by the program Headstart of Eit Health (European Union) to execute the project 'ARTHEx-DM1' (2020-HS-0215).. Funding awarded by EIT Health: €50,000

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IVACE CREATEC (Valencian Regional Government)

ARTHEx has received financial support from the CREATEC-CV program of GVA-IVACE for the implementation of the project "Early Preclinical Phases for the Development of an Innovative Drug Against Type 1 Myotonic Dystrophy" (MCBTA/2019/47). The objectives of this project include conducting in vitro toxicity studies to select oligonucleotides with low toxicity and conducting preliminary pharmacokinetic (PK) and pharmacodynamic (PD) studies of these oligonucleotides. The total eligible cost is €55,799.10, funded from the 2019 budget, with co-financing from the European Union through the European Regional Development Fund (FEDER).

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IVACE ASESORA (Valencian Regional Government)

ARTHEx has received financial support from the Specialized Advisory Services for the Growth of Innovative Small Businesses program of GVA-IVACE, ASESORA CV (year 2019) to execute the project "Strategic Diagnosis of Regulatory Affairs and Business Development in the ARTHEx Business Plan" (IMACEI/2019/11). The objective of this project is to carry out a specialized strategic diagnosis in the areas of intellectual property protection and the regulatory framework (FDA). The total eligible cost is €48,883.00, funded from the 2019 budget, with co-financing from the European Union through the European Regional Development Fund (FEDER).

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