DMPK

-ATX-01 is the industry’s first anti-microRNA therapeutic to be investigated in DM1 – VALENCIA, Spain I October 18, 2024 I ARTHEx Biotech S.L., a clinical-stage biotechnology company focused on developing innovative medicines through the modulation of gene expression, announced today that the first participant has been dosed in the Randomized Placebo Controlled Double Blind Phase I-IIa ArthemiR™ Trial of ATX-01 for Myotonic Dystrophy Type 1 (DM1). DM1 is a devastating rare neuromuscular disorder that causes muscle weakness and other life-limiting complications. There are currently no disease-modifying treatments approved for DM1. ATX-01, the industry’s first anti-microRNA therapeutic to be evaluated for DM1, targets microRNA 23b (miR-23b) which is known to be a regulator of the expression of muscle blind like (MBNL) proteins that are essential for the correct expression (splicing) of many messenger ribonucleic acids (mRNAs) and hence proteins, in the body. DM1 pathogenesis is caused by sequestration of MBNL by toxic dystrophia myotonica protein kinase (DMPK) mRNA in the nucleus, and by translational repression of MBNL production caused by miR-23b overexpression, both of which lead to a net decrease of MBNL available to exert its usual regulatory functions. ATX-01 is the only therapeutic agent that acts with a dual mechanism of action, by (1) increasing MBNL production, and (2) by destabilizing the toxic DMPK foci leading to a reduction of DMPK mRNA and release of sequestered MBNL. Both factors contribute to a general increase of active MBNL levels and splicing correction. “Since the founding of ARTHEx, we have been working tirelessly to achieve our goal of creating a new therapeutic option for persons living with DM1 and their families. We are proud to have reached a major milestone in our company’s journey with the dosing of the first participant in our ArthemiR™ trial,” said Dr. Frédéric Legros, Chairman and CEO of ARTHEx. “We believe that the market opportunity for a new DM1 therapy is very attractive, given the important unmet medical need and the lack of an approved agent that is disease-modifying.” “ATX-01 is a very unique molecule – it was discovered and developed entirely in-house by ARTHEx scientists through years of engineering and execution, and we are excited about the potential of its dual mechanism of action to improve the lives of patients with DM1,” said Dr. Beatriz Llamusí, Chief Scientific Officer and Co-Founder of ARTHEx. The ArthemiR™ trial is a global Phase I-IIa double-blind, placebo-controlled, single and multiple ascending dose study in participants with classic DM1. The primary objective is to determine the safety and tolerability of ATX-01 in DM1 participants. ARTHEx will also investigate target engagement at the muscle level through biomarkers, including MBNL levels and RNA splicing index. The clinical endpoints from the trial will include measures related to muscle function, patient-reported outcomes, and quality of life measures. The plan is to enroll fifty-six participants to allow an assessment of ATX-01’s performance in this population. Dr. Judy Walker, Chief Medical Officer of ARTHEx, added, “The ArthemiR™ trial is designed to assess the safety and tolerability of ATX-01 in persons with DM1, as well as its activity on the disease pathophysiology and clinical outcomes. We are very pleased with the non-clinical safety profile of ATX-01 and are excited about moving this agent to clinic as it offers a fresh approach to the disease due to its dual mechanism of action. We sincerely hope that ATX-01 will lead to functional benefits for patients with DM1, offer a well tolerated safety profile, and improve quality of life for those with the condition. We look forward to continuing to enroll participants and initiating more sites across the globe.” Dr. Valeria Sansone, Professor of Neurology at the University of Milan, commented, “Dosing the first participant in the ArthemiR trial is a significant milestone that represents years of research and development for DM1. Initiating new clinical studies with novel treatment options like ATX-01 may be critical for patients, families and the broader community to gain additional knowledge which may help lead to better clinical outcomes and possibly an approved treatment. I am excited to evaluate ATX-01’s dual mechanism of action in the ArthemiR trial.” About ATX-01 ATX-01 is an antimiR oligonucleotide designed to target microRNA 23b (miR-23b), which is involved in the pathogenesis of DM1. It has been demonstrated, in human DM1 myoblast cell lines and in two murine models, that ATX-01 has a unique, dual mechanism of action which reduces toxic DMPK mRNA and increases MBNL protein production. ATX-01 was discovered through ARTHEx’s in-house discovery engine, which was built to identify, design and optimize novel gene expression modulators and ensure their preferential delivery to target tissues affected by the disease. About Myotonic Dystrophy Type 1 (DM1) Myotonic dystrophy type 1 (DM1) is a highly disabling disease affecting more than one million people worldwide. The condition affects muscles and other tissues (causing respiratory problems, fatigue, hypersomnia, cardiac abnormalities, severe gastrointestinal complications, and cognitive and behavioral impairment). Most commonly, it manifests during adulthood (classic DM1). Although signs and symptoms vary among affected individuals, with progression of the disease, DM1 patients experience a reduction in the ability to perform activities of daily living. Moreover, patients have a significantly shortened lifespan and there is currently no approved treatment to slow the progression of the disease. About ARTHEx Biotech ARTHEx Biotech is a clinical-stage biotechnology company focused on developing innovative medicines through the modulation of gene expression. The Company’s lead investigational compound, ATX-01, is being evaluated for the treatment of myotonic dystrophy type 1 (DM1), a rare neuromuscular disorder, in the Phase I-IIa ArthemiR™ trial. ArthemiR trial is co-funded by EIC Accelerator program under the Grant Agreement Nº 190181217. ARTHEx is advancing its in-house discovery engine to identify and develop nucleic acid-based therapies for other disorders with high unmet medical need, including genetically-driven diseases. The Company headquarters are in Valencia, Spain. For more information, please visit www.arthexbiotech.com and engage with us on LinkedIn. SOURCE: ARTHEx Biotech

-Study highlights dual targeting action, demonstrating significant therapeutic potential for treating myotonic dystrophy type 1 (DM1) across a variety of disease severities – VALENCIA, Spain, Oct. 16, 2024 /PRNewswire/ -- ARTHEx Biotech S.L., a clinical-stage biotechnology company focused on developing innovative medicines through the modulation of gene expression, today announced a publication in Science Advances showcasing the dual mechanism of two anti-miRs, offering a promising therapeutic avenue in myotonic dystrophy type 1 (DM1) by addressing the reduced free Muscle-Blind Like Splicing regulator (MBNL) proteins due to sequestration in DMPK mRNA foci and due to reduced production. "This published research demonstrates the promising potential of RNA therapeutics to address the underlying disease-driving mechanisms of DM1," said Beatriz Llamusi, PhD, Chief Scientific Officer and Co-Founder of ARTHEx Biotech. "We are pleased to have our science recognized by a high-quality journal like Science Advances and we look forward to realizing the potential impact of our approach on DM1 scientific research." This study described in the publication evaluated the potential therapeutic efficacy of two AntimiRs in primary myoblasts derived from patients with DM1. DM1, caused by unstable CTG repeat expansions in the DMPK gene, leads to muscle defects due to depletion of the crucial splicing regulator protein MBNL1. AntimiRs specifically targeting miR-23b and miR-218, which are natural repressors of MBNL1, demonstrated significant reductions in toxic DMPK mRNA, restoring normal MBNL1 levels and correcting critical cellular defects such as myoblast fusion, myotube formation and reversing splicing defects. Notably, the AntimiR-23b treatment reduced DMPK transcripts and reversed 68% of dysregulated genes, and did so across various forms of DM1, independent of the CTG repeat size, suggesting broad potential. These findings underscore the dual mechanism of AntimiR-23b, offering a promising therapeutic avenue by addressing MBNL1 depletion due to both DMPK accumulation and sequestration, as well as reduced production. The published manuscript, titled "AntimiR treatment corrects myotonic dystrophy primary cell defects across several CTG repeat expansions with a dual mechanism of action", is available online. About Myotonic Dystrophy Type1 (DM1) Myotonic dystrophy type 1 (DM1) is a highly disabling disease affecting more than one million people worldwide. The condition affects muscles and other tissues (causing respiratory problems, fatigue, hypersomnia, cardiac abnormalities, severe gastrointestinal complications, and cognitive and behavioral impairment). Most commonly, it manifests during adulthood (classic DM1), although DM1 can develop at birth in a congenital form, or during childhood. Although signs and symptoms vary among affected individuals, sadly, with progression of the disease, DM1 patients experience a reduction in the ability to perform activities of daily living. Moreover, patients have a significantly shortened lifespan and there is currently no approved treatment to slow the progression of the disease. About ARTHEx Biotech ARTHEx Biotech is a clinical-stage biotechnology company focused on developing innovative medicines through the modulation of gene expression. The Company's lead investigational compound, ATX-01, is being evaluated for the treatment of myotonic dystrophy type 1 (DM1), a rare neuromuscular disorder, in the Phase I-IIa ArthemiR™ trial. ARTHEx is also advancing its in-house discovery engine to identify and develop gene expression modulators for other disorders with high unmet medical needs, including genetically-driven diseases like DM1. The Company headquarters are in Valencia, Spain. For more information, please visit and engage with us on LinkedIn. Company Contact Frédéric Legros Executive Chairman and CEO [email protected] +33679495790 Investor and Media Contact Amy Conrad Juniper Point [email protected] +1 858-366-3243 SOURCE ARTHEx Biotech WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Earlier this year, Avidity started a pivotal Phase III HARBOR trial evaluating del-desiran inpatients with DM1. Image credit: JHVEPhoto /Shutterstock. The US Food and Drug Administration (FDA) has lifted the partial clinical hold on Avidity Biosciences ’ investigational drug, delpacibart etedesiran (del-desiran). In 2022, the US regulatory agency placed a partial hold after a report of a serious adverse event in a newly enrolled patient in the Phase I/II MARINA trial (NCT05027269), which evaluated del-desiran in patients myotonic dystrophy type 1 (DM1). The company did not disclose the details of the adverse event and the US FDA eased the partial clinical hold the following year, allowing the company to recruit new patients. The clinical hold has not slowed down Avidity’s efforts to advance the clinical development of del-desiran in DM1. Earlier this year, Avidity started a pivotal placebo-controlled Phase III HARBOR trial (NCT06411288). The study is expected to enrol 150 participants with DM1 who will be assessed over 54 weeks. The trial’s primary endpoint is the improvement of myotonia over 30 weeks, measured using video Hand Opening Time (vHOT), the average time to extend the right third and first digits. The study’s secondary endpoints also include the functional assessment of myotonia across 30 weeks, including hand grip strength, quantitative muscle testing composite score and Myotonic Dystrophy Type 1 activity and participation scale c. Del-desiran is an antibody oligonucleotide conjugate (AOC) made up of a monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a small interfering RNA (siRNA) targeting myotonic dystrophy protein kinase (DMPK) mRNA, responsible for producing DMPF protein. If approved, GlobalData expects del-desiran to pull in over $1.2bn in sales by 2030. See Also: BMS receives FDA approval for Opdivo to treat NSCLC Novaliq and Laboratoires Théa announce EC approval for dry eye disease therapy GlobalData is the parent company of Pharmaceutical Technology . mRNA vaccines were instrumental during the Covid-19 pandemic. Since then, there has been increased interest in mRNA therapies beyond the vaccines. GlobalData forecasts the mRNA non-vaccine therapeutics field to reach $2bn by 2028. DM1 is a genetic disorder caused by a triplet-repeat in the DMPK gene. It primarily affects skeletal and cardiac muscle causing muscle weakness and wasting leading to respiratory problems, and cardiac abnormalities. There are no approved treatments for DM1 and management is mostly aimed at symptomatic treatment. Another therapy in development for treating DM1 is AMO Pharma’s AMO-02 (tideglusib). The therapy is an irreversible inhibitor of glycogen synthase kinase 3 (GSK-3), it has the potential to disrupt the RNA repeats that cause congenital DM1. In May, AMO announced plans to start a Phase III trial for AMO-02 in DM1 patients.