Periodic Reporting for period 1 - fight-dm1 (First In class oliGo THerapy for Myotonic Dystrophy type 1 (DM1))
Berichtszeitraum: 2023-01-01 bis 2024-03-31
FIGHT-DM1 is a project aimed at developing, ATX-01, a first-in-class oligo therapy for myotonic dystrophy type 1 (DM1). In order to relieve the health-related pains of patients, our project aims to clinically validate our proposed product, ATX-01, as a disruptive disease-modifying therapy for myotonic dystrophy type 1. We aim to impact the quality of life of DM1 patients by relieving their symptoms and slowing the disease progression, while also contributing to significant economic savings for their families and healthcare systems.
About ATX-01
ATX-01 is an antimiR oligonucleotide designed to target microRNA 23b (miR-23b), which is associated with regulating the expression of MBNL proteins involved in the pathogenesis of DM1. It has been demonstrated in human DM1 myoblast cell lines that ATX-01 has a unique, dual mechanism of action which reduces toxic DMPK mRNA and increases MBNL protein levels. Toxic DMPK and reduced levels of MBNL have been identified as the molecular underpinnings of DM1. ATX-01 is being evaluated in the Phase I-IIa ArthemiR™ trial for the treatment of DM1. ATX-01 has received Orphan Drug Designation for ATX-01 in DM1 from the US and European authorities.
ATX-01 was discovered through ARTHEx’s in-house discovery engine, which is designed to identify and optimize novel microRNA modulators and ensure their preferential delivery to target tissues, for the treatment of diseases in which microRNAs are involved in the disease pathogenesis.
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 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 ATX-01
ATX-01 is an antimiR oligonucleotide designed to target microRNA 23b (miR-23b), which is associated with regulating the expression of MBNL proteins involved in the pathogenesis of DM1. It has been demonstrated in human DM1 myoblast cell lines that ATX-01 has a unique, dual mechanism of action which reduces toxic DMPK mRNA and increases MBNL protein levels. Toxic DMPK and reduced levels of MBNL have been identified as the molecular underpinnings of DM1. ATX-01 is being evaluated in the Phase I-IIa ArthemiR™ trial for the treatment of DM1. ATX-01 has received Orphan Drug Designation for ATX-01 in DM1 from the US and European authorities.
ATX-01 was discovered through ARTHEx’s in-house discovery engine, which is designed to identify and optimize novel microRNA modulators and ensure their preferential delivery to target tissues, for the treatment of diseases in which microRNAs are involved in the disease pathogenesis.
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 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.
The FIGHT DM-1 project is intended to evaluate the safety, tolerance, pharmacokinetics, pharmacodynamics and clinical effectiveness of ATX-01 in patients with DM1 by conducting the ArthemiRTM clinical trial. In addition, chronic non-clinical studies are being performed to support future long-term clinical trials.
Concerning the clinical development of ATX-01, all necessary study start-up activities are ongoing to request authorization for the initiation of the clinical trial from the respective regulatory authorities. The ArthemiRTM clinical study has received IND clearance from the US FDA and Health Canada to start the study. Applications to the European authorities (CTIS application) and the UK MHRA are being evaluated. As a result, we expect the first site to be fully activated and ready to enroll study participants by Q2 24 in the USA.
In a parallel effort, the GMP batch of Investigational Medicinal Product (active and placebo) has been manufactured, being ready for its Investigational use.
Finally, Arthex has obtained Orphan Drug Designation (ODD) from both the FDA and EMA for ATX-01 in the treatment of DM1. ODD status will open the door for significant benefits to the development of ATX-01. Arthex will carry out all the necessary regulatory activities for the future renewal of this status in the framework of the FIGHT-DM1 project.
Concerning the clinical development of ATX-01, all necessary study start-up activities are ongoing to request authorization for the initiation of the clinical trial from the respective regulatory authorities. The ArthemiRTM clinical study has received IND clearance from the US FDA and Health Canada to start the study. Applications to the European authorities (CTIS application) and the UK MHRA are being evaluated. As a result, we expect the first site to be fully activated and ready to enroll study participants by Q2 24 in the USA.
In a parallel effort, the GMP batch of Investigational Medicinal Product (active and placebo) has been manufactured, being ready for its Investigational use.
Finally, Arthex has obtained Orphan Drug Designation (ODD) from both the FDA and EMA for ATX-01 in the treatment of DM1. ODD status will open the door for significant benefits to the development of ATX-01. Arthex will carry out all the necessary regulatory activities for the future renewal of this status in the framework of the FIGHT-DM1 project.
The ArthemiR™ trial is a Phase I-IIa double-blind, placebo-controlled, dose-escalation study expected to enroll participants with classic Myotonic Dystrophy Type 1 (DM1).
The anticipated outcomes include establishing the safety and tolerability profile of both single and multiple ascending doses of ATX-01 in individuals with DM1. Besides, ARTHEx expects to anticipate potentially uncovering insights into target engagement at the muscle level. Additionally, the trial's clinical endpoints are expected to reveal improvements in muscle function, patient-reported outcomes, and overall quality of life, thereby demonstrating the potential impact of the treatment.
On the other hand, by executing the chronic toxicity studies would allow the chronic administration of the drug in humans.
The successful execution of the project will pave the way for the next clinical phase of development towards the drug approval process.
The impact of the FIGHT-DM1 project is substantial, especially for those affected by DM1 and their environment. DM1 is the most prevalent adult-onset muscular dystrophy and there are more than 100.000 DM1 diagnosed patients in the US and EU. There are no curative treatments to date, and the only available solutions for this seriously debilitating and life-threatening disease are palliative treatments. ATX-01 has the potential to become an effective disease modifying treatment for DM1.
Moreover, the long-term benefits of our therapy could be expected to potentially relieve the symptoms of DM1 patients, slow the disease progression, increase their quality of life, increase their life expectancy and, ultimately, facilitate the integration of DM1 patients into society.
Finally, our solution would have an impact on healthcare systems. ATX-01 has the potential to reduce the average costs that both healthcare systems and families face in caring for DM1 patients.
Key needs to ensure further success:
Successful execution of the FIGHT-DM1 project is essential to advance to the next phase towards the drug approval. This important milestone would potentially allow ATX-01 to be available as a disease-modifying treatment for DM1.
For ARTHEX, preliminary results within the framework of the project will enable us to secure additional funding to advance the clinical development of ATX-01 and execute our business plan.
What is more, the project is bolstering our intellectual property by reinforcing our patent portfolio.
The anticipated outcomes include establishing the safety and tolerability profile of both single and multiple ascending doses of ATX-01 in individuals with DM1. Besides, ARTHEx expects to anticipate potentially uncovering insights into target engagement at the muscle level. Additionally, the trial's clinical endpoints are expected to reveal improvements in muscle function, patient-reported outcomes, and overall quality of life, thereby demonstrating the potential impact of the treatment.
On the other hand, by executing the chronic toxicity studies would allow the chronic administration of the drug in humans.
The successful execution of the project will pave the way for the next clinical phase of development towards the drug approval process.
The impact of the FIGHT-DM1 project is substantial, especially for those affected by DM1 and their environment. DM1 is the most prevalent adult-onset muscular dystrophy and there are more than 100.000 DM1 diagnosed patients in the US and EU. There are no curative treatments to date, and the only available solutions for this seriously debilitating and life-threatening disease are palliative treatments. ATX-01 has the potential to become an effective disease modifying treatment for DM1.
Moreover, the long-term benefits of our therapy could be expected to potentially relieve the symptoms of DM1 patients, slow the disease progression, increase their quality of life, increase their life expectancy and, ultimately, facilitate the integration of DM1 patients into society.
Finally, our solution would have an impact on healthcare systems. ATX-01 has the potential to reduce the average costs that both healthcare systems and families face in caring for DM1 patients.
Key needs to ensure further success:
Successful execution of the FIGHT-DM1 project is essential to advance to the next phase towards the drug approval. This important milestone would potentially allow ATX-01 to be available as a disease-modifying treatment for DM1.
For ARTHEX, preliminary results within the framework of the project will enable us to secure additional funding to advance the clinical development of ATX-01 and execute our business plan.
What is more, the project is bolstering our intellectual property by reinforcing our patent portfolio.