The approval of several pipeline agents will drive growth in the non-vaccine mRNA therapeutics landscape by 2028, according to GlobalData’s upcoming Thematic Research: mRNA Therapeutics report. There are currently no marketed non-vaccine mRNA therapeutics in any of the seven major markets (7MM), which include the US, France, Germany, Italy, Spain, and the UK (5EU), and Japan. However, there has been a surge of interest in the mRNA therapeutics space after the Covid-19 pandemic wherein mRNA vaccines proved successful.

Now, pharma companies such as Moderna , Ultragenyx , Omega Therapeutics , and BioNTech are further exploring mRNA therapeutics for cancer and rare genetic diseases. There are five non-vaccine mRNA therapeutics in clinical trial development, all in Phase I/II. Their combined revenue is estimated to be upwards of $2bn by 2028, with Ultragenyx’s OTX-2002 contributing most significantly to sales, generating $1.6bn during 2028, according to analyst consensus forecasts on GlobalData’s Pharma Intelligence Centre.

OTX-2002 is under development by Omega Therapeutics for hepatocellular carcinoma and solid tumours. The candidate is a myc proto-oncogene protein inhibitor and functions as an epigenomic controller. The candidate is delivered as mRNA to modulate gene expression. Moderna is currently developing two non-vaccine mRNA therapeutics: mRNA-3705 for methylmalonic acidemia, and mRNA-3927 for propionic acidemia. Both of these indications are rare genetic disorders and the anticipated revenue from each candidate is $491m and $278m, respectively.

Another rare genetic disease that is being explored is glycogen storage disorder type III, or Cori’s disease. Ultragenyx’s LUNAR-GSD3/UX053 aims to address the tissue accumulation of abnormally structured glycogen seen in Cori’s disease through its glycogen debranching enzyme replacement therapy. The final non-vaccine mRNA therapeutic in Phase I/II is BioNTech’s BNT-141, a claudin18.2 inhibitor. By inhibiting claudin18.2, the drug candidate elicits anti-tumour activity. BioNTech’s pipeline drug is in development for ovarian cancer, bile duct cancer (cholangiocarcinoma), adenocarcinoma of the gastroesophageal junction, colorectal cancer, pancreatic cancer, and solid tumours.

Opportunities within the mRNA therapeutics landscape include:

  • Restoration of gene expression without the risk of genomic integration
  • Ability to repeat and adjust doses and dose intervals
  • Minimal changes to the manufacturing process for multiple targets
  • Ability to act on targets that are otherwise ‘undruggable’ for small molecules
  • Relatively high transfection efficiency and low toxicity given that mRNA does not need to enter the nucleus to be function

Barriers within the mRNA therapeutics landscape include:

  • Instability as mRNA is susceptible to degradation by ribonucleases
  • Lipid nanoparticles must be tissue-specific and biodegradable
  • Risk of activating the immune system
  • Difficult to achieve high quality and purity of mRNA with scalable manufacturing
  • Need for periodic reapplication of drug for effects to be sustained

Cell & Gene Therapy coverage on Clinical Trials Arena is supported by Cytiva.

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