Table 2

Biopharmaceutical companies developing mRNA therapeutics for metabolic diseases and coagulation disorders targeting the liver

CompanyDelivery systemModalityDiseaseTherapeutic mRNA (reference)Trial phase current statusPublication/website
Translate Bio (Lexington, MA, USA)LNPsSystemic intracellular therapeuticsOrnithine transcarbamylase deficiencyOTC (MRT5201)Phase I/II clinical trial (NCT03767270); IND enabling start date: March 2019 https://translate.bio
PhaseRx (Seattle, WA, USA)Polymer micelle + LNP: Proprietary
PhaseRx
Systemic intracellular therapeuticsOrnithine transcarbamylase deficiencyOTC (PRX-0D2)PreclinicalRef 20
CureVac (Tübingen, Germany) + Arcturus TherapeuticsLipid-mediated nucleic acid deliverySystemic intracellular therapeuticsOrnithine transcarbamylase deficiencyLUNAR-OTCPreclinical https://www.curevac.com
Moderna Therapeutics (Cambridge, MA, USA)LNP: Proprietary
Moderna Therapeutics
Systemic intracellular therapeuticsMethylmalonic acidaemiaMUT (mRNA-3704)Phase I/II clinical trial (NCT03810690) Estimated start date: May 2019.Ref 8
Moderna Therapeutics (Cambridge, MA, USA)LNP: Proprietary
Moderna Therapeutics
Systemic intracellular therapeuticsAcute intermittent porphyriaPBGDPreclinicalRef 9
Moderna Therapeutics (Cambridge, MA, USA)LNP: Proprietary
Moderna Therapeutics
Systemic intracellular therapeuticsPropionic acidaemiaPCCA + PCCB (mRNA-3927)Preclinical https://www.modernatx.com
Moderna Therapeutics (Cambridge, MA, USA)LNP: Proprietary
Moderna Therapeutics
Systemic intracellular therapeuticsPhenylketonuriaPAH (mRNA-3283)Preclinical https://www.modernatx.com
Shire Pharmaceuticals (Lexington, MA, USA)Cationic lipidoid C12-200-based LNP formulationSystemic secreted therapeuticsAnaemia in haemophilia BhEPOPreclinicalRef 64 64
Shire Pharmaceuticals (Lexington, MA, USA)Cationic lipidoid C12-200-based LNP formulationSystemic secreted therapeuticsHaemophilia BhFIXPreclinicalRef 64
65
Arcturus Therapeutics (San Diego, CA, USA)LNP: Proprietary
Arcturus Therapeutics
Systemic secreted therapeuticsHaemophilia BLUNAR LNP-hFIX mRNAPreclinicalRef 65
Arbutus Biopharma (Vancouver, BC, Canada) and Genevant Sciences (Burnaby, BC, Canada)Lipid nanoparticle (LNP) + ligand conjugate deliverySystemic intracellular therapeuticsRare genetic disorders (ND until 2020)NDPreclinical https://arcturusrx.com
  • hEPO, human erithropoietin; hFIX, human factor IX; IND, investigational new drug; LUNAR, lipid-enabled and unlocked nucleomonomer agent modified RNA; MUT, mutase; ND, not disclosed; OTC, ornithine transcarbamylase; PAH, phenlalanine hydroxylase; PBGD, porphobilinogen deaminase; PCCA, propionyl-CoA carboxylase subunit A; PCCB, propionyl-CoA carboxylase subunit B.