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Purpose of the study
The purpose of this first-in-human trial is to demonstrate the safety and first efficacy of the cell and gene therapy product Satgeno-01. The aim is to verify if Satgeno-01 can provide a regenerative gene correction therapy for Limb Girdle Muscular Dystrophy Type 2A (LGMD2A) patients bearing the CAPN3 c.550delA variant (carrying either one or two copies).
Satgeno-01 are patient-derived gene edited primary human satellite cell-derived muscle stem cells (Gen-PHSats) developed towards an advanced therapy medicinal product (ATMP) to deliver for the first time gene repair therapy to skeletal muscle and initiate healthy muscle formation by cured muscle stem cells in the muscle of LGMD2A patients.
DELI550 Timeline
Predicted Clinical Development Satgeno-01 for LGMD2A
Current Status*: Please note that we are in the preclinical preparation phase for the conduction of the clinical trial.
Next steps include proving successful pharmaceutical grade GMP manufacturing of gene edited primary muscle stem cells and the clinical trial application at the regulatory authorities.
As soon as we are closer to starting the trial we will inform patient organizations and clinical experts.
There is no recruitment taking place at the moment.
Recruitment will be then initiated by the study center.
Satgeno Patient Journey
SATGENO is being established as an autologous therapy that uses genetically corrected Primary Human Satellite cell-derived muscle stem cells (Gen-PHSats) to treat muscular dystrophies.
Cells are isolated from a small muscle biopsy specimen of the patients. The disease-causing mutation is repaired with specific gene editing tools.
The repaired cell population is expanded with a novel PHSats technology and injected into selected affected muscles to build healthy muscle tissue and provide muscle stem cells for long-term regeneration.
A first-in-human clinical trial is currently prepared.
SATGENO Platform
With Satgeno-01 a single mutation in the CAPN3 gene is being corrected. The DELI550 clinical trial will pave the way to establish the SATGENO platform: In proving safety and demonstrating first efficacy of Satgeno-01, the aim is to successively target new disease-causing mutations, and in the future treat a comprehensive spectrum of muscular dystrophies.
Partners involved
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Limb-girdle muscular dystrophies (LGMDs) are a group of over 30 inherited monogenetic disorders characterized by progressive muscle wasting and weakness primarily in the shoulder and pelvic girdle areas. Disease onset is in childhood or teens, and may involve in some subtypes cardiopulmonary complications. There are currently no authorised therapies that can stop or reverse disease progression. Disease management is dependent therefore on symptomatic treatment only and includes mainly physical therapy.
The most prevalent subtype is LGMD2A (also named LGMDR1) which arises from mutations in the CAPN3 gene, encoding Calpain 3, a calcium-dependent muscle-specific cysteine proteasea. Close to 70,000 patients worldwide are affected by this autosomal recessive gene defectb. Disease onset is usually at the beginning of the second decade of life with severe muscle atrophy. Patients lose their ability to walk independently usually within 15 years. Numerous disease-causing mutations across the entire length of the CAPN3 gene have been described.
Please note: Myopax’ first Satgeno-01 product is targeting a founder mutation named CAPN3 c.550delAc. A clinical trial is underway named DELI550 directed towards a first-in-human application of Satgeno-01.
Advanced Therapy Medicinal Products (ATMPs) are a class of innovative therapies that are based on genes, tissues or cells. ATMPs fall under stringent EU and international regulatory frameworks, requiring advanced manufacturing standards (GMP for ATMPs), defined clinical documents, and long-term follow-up. They must be developed under specific regulatory pathways, including scientific advice and centralized marketing authorization through the European Medicines Agency (EMA).
The EMA classifies ATMPs as follows:
- Gene therapy medicine – introduce genetic material into a patient’s cells to treat or prevent disease.
- Somatic-cell therapy medicine – contain cells or tissues that have been manipulated to change their biological characteristics.
- Tissue-engineered medicines – contain cells or tissues used to regenerate, repair, or replace human tissue.
Please note: Satgeno-01 is a combined gene therapy and tissue engineered product.
Gene editing refers to a range of new molecular biological techniques that can be used to make targeted alterations to the genome by inserting, replacing or deleting a DNA sequence with the aim to correct disease-causing mutations. The rapid development of such methods represent the CRISPR/Cas systems that allow for targeting defined regions of the genome. The SATGENO platform uses CRISPR variations aiming for precise, efficient and safe repair of mutations in genes encoding therapeutically relevant muscle proteins. Which CRISPR tool is used depends on the type of the specific disease-causing mutation.
The gene editing tools are delivered in the SATGENO platform in the form of mRNA into patients’ own muscle stem cells making the toolkit safer and well controllabled.
Please note: Myopax’ first Satgeno-01 product is targeting a founder mutation named CAPN3 c.550delA that is repaired by Cas9.
Stem cells are unspecialized cells with the unique ability to self-renew (create more stem cells) and to become many different types of specialized cells (like muscle, nerve or blood cells) serving as a natural repair system for the body. Stem cells are essential for development and the replacement of damaged or aged cells in tissues and organs.
Different types of stem cells reside in specific tissues throughout the body, each fulfilling specialized roles in maintaining tissue homeostasis and enabling repair after injury.
In skeletal muscle highly specialized muscle stem cells are responsible for muscle growth, maintenance and repair throughout life. In a healthy, uninjured muscle, the muscle stem cell reside dormant in their niche. When the muscle is injured, the “regeneration signal” is triggered and musce stem cells become activated. They start to divide asymmetrically: some cells regenerate the muscle; others repopulate the stem cell niche.
The muscle structure of patients with muscular dystrophies is more unstable, since structurally important proteins are either not formed or formed incorrectly. The muscle tissue is in a state of chronic injury, where stem cells are constantly activated leading to the depletion of the stem cell pool and consequent failure of the regeneration. The muscle tissue is irreversibly reorganized into adipose and connective tissue.
Please note: Satgeno-01 provides repaired muscle stem cells that can build healthy muscle tissue and refill the muscle’s own stem cell pool offering long-term therapeutic effect.
Clinical trials are systematic investigations in which new medical interventions like drugs, therapies or devices are tested in humans to assess their efficacy, safety, and tolerability. The regulatory authority approval and ethic committee positive opinion is mandatory prior to start. Study conduct is controlled until the end of the trial to ensure adherence to study defined requirements (e.g. defined criteria for in- and exclusion of study participants or data monitoring).
Phases of Clinical Trials in Orphan Diseases (like for example the rare disease LGMD)
Preclinical Phase
Laboratory research using animal models or cell models provides robust data on safety and efficacy of the intervention.
Phase 1
Test a new treatment for the first time in a small group of patients and evaluate its safety.
Phase 2
Further evaluate safety and demonstrate efficacy in a small group of patients with the disease and determine effective dose.
Phase 3
Post-authorization Phase
Collect more comprehensive data on the drug’s efficacy, safety, and long-term effects.
Conditional market approval
Approval can be obtained after Phase 2 under expedite pathways, with Phase 3 thereafter serving as post market surveillance.
