Methylmalonic acidemia (MMA), known as methylmalonic aciduria, is a cluster of inherited disorders caused by mutations in genes that are inherited in an autosomal recessive manner. Individuals with methylmalonic acidemia are unable to process certain proteins and fat parts properly, resulting in the accumulation of methylmalonic acid (toxic substances) in the blood and/or urine and a serious condition known as decompensation events or metabolic crises. There is currently no approved treatment for methylmalonic acidemia.
Deficiency of the enzyme methylmalonic acid-CoA mutase (encoded by the human MUT gene) is the major cause of methylmalonic acidemia (about 60% of cases), and enzyme replacement therapy or MUT mRNA-based therapies provide the drugs of choice.
mRNA-3704 and mRNA-3705
In animal models, preclinical proof-of-concept studies have presented that mRNA therapies are also indicated for the treatment of rare metabolic disorders such as isolated methylmalonic acidemia (MMA). mRNA-3704 and mRNA-3705, two mRNA-based MMA therapy candidates, were discovered by Moderna, encoding for functional methylmalonyl-CoA mutase enzyme. mRNA-3704 and mRNA-3705 are formulated with lipid nanoparticle (LNP).
mRNA-3705 is currently under clinical trials. It has been reported that mRNA-3705 has been tested in a Phase 1/2 study (Landmark study) in which 11 participants received 221 doses of mRNA-3705. To date, all participants have elected to participate in a subsequent Open-Label Extension study. Till now, mRNA-3705 has generally gained well-tolerating ability and no studies have been discontinued due to safety or meeting protocol-defined dose-limiting toxicity criteria.
Yaohai Bio-Pharma Offers One-Stop Solution for RNA
Custom Deliverables
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Grade
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Deliverables
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Specification
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Applications
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non-GMP
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Drug Substance, mRNA
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0.1~10 mg (mRNA)
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Preclinical research such as cell transfection, Analytical method development, Pre-stability studies, Formulation development
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Drug Product, LNP-mRNA
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GMP, Sterility
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Drug Substance, mRNA
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10 mg~70 g
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Investigational new drug (IND), Clinical trial authorisation (CTA), Clinical trial supply, Biologic license application (BLA), Commercial supply
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Drug Product, LNP-mRNA
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5000 vials or pre-filled syringes/ cartridges
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mRNA Therapeutics Pipelines for Methylmalonic Acidemia
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Code Name
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Target Protein
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Indications
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Manufacturer
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Latest Stage
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mRNA-3705
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Methylmalonyl-CoA mutase
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Methylmalonic acidemia
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Moderna
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Phase II
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mRNA-3704
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Methylmalonyl-CoA mutase
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Methylmalonic acidemia
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Moderna
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Phase I/II
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