mRNA-based drug approaches Phase I milestone

Moderna and partner AstraZeneca have filed paperwork to advance the first 'secreted protein' mRNA drug into Phase I trials. Initiation of the trial will be an important test for a new drug modality that aims to selectively boost the production of proteins of interest.

The partners' drug, AZD8601, consists of a modified form of the mRNA that encodes vascular endothelial growth factor A (VEGFA). “We believe that using modified mRNA to initiate a strong, local and transient surge of VEGFA expression could help us overcome challenges associated with previous approaches to regulate this protein in tissues,” said Marcus Schindler, AstraZeneca's Vice President of Innovative Medicines and Early Development, in a statement. Because VEGFA modulates the fate of cardiac progenitor cells, AZD8601 might provide a regenerative treatment option for patients with heart failure, diabetic wound healing and other ischaemic vascular diseases.

Earlier this year Moderna also advanced mRNA 1440 and mRNA 1851, two infectious disease mRNA vaccines against undisclosed indications, into the clinic. Whereas AZD8601 aims to increase levels of a functional, secreted host protein, mRNA vaccines are typically used to generate pathogenic antigens and the resulting protective antibodies (Nat. Rev. Drug Discov. 15, 521–522; 2016).

Moderna has been criticized for being tight-lipped about the science behind its mRNA-based drugs (Nature 522, 26–28; 2015). A key question is how they have overcome delivery hurdles to get their drugs into the relevant cell and tissue types. The company has said that it will become more transparent as its programmes move through the clinic. Moderna plans to have six candidates in the clinic by the end of the year. Other areas of interest for Moderna include rare diseases and immuno-oncology (Nat. Rev. Drug Discov. 14, 378–379, 2015). The company is developing candidates independently and in collaboration with industry partners, including Alexion, Merck & Co. and Vertex.