Technology - Myopax

PHSat manufacture

Our core technology is our patented method for the isolation and cultivation of regenerative muscle stem cells.

This enables us to produce large high-purity populations of stem cells that we call PHSats: Primary Human Satellite cell derived muscle stem cells. In contrast to conventionally cultured muscle cells, PHSats retain the regenerative capacity of satellite cells.

From just a few grammes of tissue, more than 100 million pharmaceutical quality PHSats can be produced. In preclinical studies PHSats built new muscle tissue and repopulated the stem cell niche, thereby providing both short and long-term regenerative effects.

In patients with local muscle defects, this technology enables effective autologous treatment.

Pipeline

Bekele et al., 2022. Human primary muscle stem cells regenerate injured urethral sphincter in athymic rats. Animal Model Exp Med.

Marg et al., 2019. Human muscle-derived CLEC14A-positive cells regenerate muscle independent of PAX7. Nat Commun.

Marg et al., 2014. Human satellite cells have regenerative capacity and are genetically manipulable. J Clin Invest.

Muscle stem cell engineering from iPSCs

The PHSats phenotype is our target for cell engineering. Now we are engineering PHSats-analogs that meet disease-specific needs.

Induced pluripotent stem cells (iPSCs) are precursor cells that can differentiate into muscle stem cells. Their ubiquity makes them ideal for cell engineering. From iPSCs we are engineering PHSats-analogs that are universally immunologically tolerable and can be used for allogenic therapies.

Our engineered PHSats will be available as “off-the-shelf” products for the treatment of acute muscle atrophy.

Pipeline

Metzler et al., 2022. Generation of hiPSC-Derived Skeletal Muscle Cells: Exploiting the Potential of Skeletal Muscle-Derived hiPSCs. Biomedicines.

Metzler et al., 2020. Generation of three age and gender matched pairs of human induced pluripotent stem cells derived from myoblasts (MDCi011-A, MDCi012-A, MDCi013-A) and from peripheral blood mononuclear cells (MDCi011-B, MDCi012-B, MDCi013-B) from the same donor. Stem Cell Res.

Metzler et al., 2020. Generation of two human induced pluripotent stem cell lines derived from myoblasts (MDCi014-A) and from peripheral blood mononuclear cells (MDCi014-B) from the same donor. Stem Cell Res.

mRNA-delivered gene repair

The delivery of genetically repaired PHSats will be a groundbreaking development in the treatment of muscular dystrophies providing both immediate and long-term regeneration of functionally critical muscles.

We have developed mutation specific gene-editing toolkits based on CRISPR/Cas technology that ensure precise, efficient and safe repair of mutations in genes encoding therapeutically relevant muscle proteins. When combining our patented PHSats expansion process with GMP-compliant mRNA delivery of the repair toolkit, the patient’s own stem cells can be cured.

Pipeline

Müthel et al., 2023. Cas9-induced single cut enables highly efficient and template-free repair of a muscular dystrophy causing founder mutation. Mol Ther Nucleic Acids.

Wang et al., 2023. LMNA Co-Regulated Gene Expression as a Suitable Readout after Precise Gene Correction. Int Mol J Sci.

Arnold & Webster. 2022. 11 clinical trials that will shape medicine in 2023. Nature Medicine

Stadelmann et al., 2022. mRNA-mediated delivery of gene editing tools to human primary muscle stem cells. Mol Ther Nucleic Acids.

Escobar et al., 2021. Base editing repairs an SGCA mutation in human primary muscle stem cells. JCI Insight.

Behaviour of muscle stem cells in conventional culture

Satellite cells are the true stem cells of skeletal muscle and are essential for growth, maintenance, and regeneration of the tissue.

When extracted from their local niche in muscle and cultivated using conventional methods, these cells quickly differentiate and fuse into myotubes (the precursors of myofibers), thereby losing their regenerative and proliferative characteristics. Conventional culture methods can also lead to the satellite cells beginning as a minority population amongst other co-isolated cell types and being quickly overgrown. Therefore, conventional culture methods are unsuitable for pharmaceutical expansion processes since the resultant populations lack the purity and potency essential for therapeutic efficacy.

Müthel et al., 2023. Cas9-induced single cut enables highly efficient and template-free repair of a muscular dystrophy causing founder mutation. Mol Ther Nucleic Acids.

Wang et al., 2023. LMNA Co-Regulated Gene Expression as a Suitable Readout after Precise Gene Correction. Int Mol J Sci.

Bekele et al., 2022. Human primary muscle stem cells regenerate injured urethral sphincter in athymic rats. Animal Model Exp Med.

Metzler et al., 2022. Generation of hiPSC-Derived Skeletal Muscle Cells: Exploiting the Potential of Skeletal Muscle-Derived hiPSCs. Biomedicines.

Stadelmann et al., 2022. mRNA-mediated delivery of gene editing tools to human primary muscle stem cells. Mol Ther Nucleic Acids.

Escobar et al., 2021. Base editing repairs an SGCA mutation in human primary muscle stem cells. JCI Insight.

Marg et al., 2019. Human muscle-derived CLEC14A-positive cells regenerate muscle independent of PAX7. Nat Commun.

Marg et al., 2014. Human satellite cells have regenerative capacity and are genetically manipulable. J Clin Invest.

Proprietary technologies support our cell therapy platforms

Three pillars of state-of-the-art technology support the platforms upon which we develop first-in-class therapeutics for targeted muscle disease indications.

Our core technology is our patented method for the isolation and cultivation of regenerative muscle stem cells.

The PHSats phenotype is our target for cell engineering. Now we are engineering PHSats-analogs that meet disease-specific needs.

The delivery of genetically repaired PHSats will be a groundbreaking development in the treatment of muscular dystrophies providing both immediate and long-term regeneration of functionally critical muscles.

Are you an investor, pharmaceutical company or preclinical developer?