Moderna Doses First Patient in Study of Autoimmune mRNA Candidate

Moderna recently dosed the first participant in the Phase 1 study of its autoimmune mRNA candidate, mRNA-6231, to expand regulatory T-cells.

The trial is the first in-human, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of mRNA-6231 in healthy adults between 18 and 50 years of age.

mRNA-6231 is the company’s modified mRNA-encoded IL-2 and the first autoimmune candidate to enter the clinic. It is also Moderna’s first subcutaneously administered therapeutic program.

“The initiation of the Phase 1 study of mRNA-6231 is an important milestone for Moderna, as we now look to bring the potential of mRNA therapeutics to people living with autoimmune diseases,” Ruchira Glaser, MD, senior vice president and therapeutic area head, rare disease, autoimmune & cardiovascular at Moderna, said in the announcement.

“This is our first mRNA autoimmune candidate, and the first to be subcutaneously administered. Today marks another important step in our mission to deliver on the promise of mRNA to help patients across diseases,” Glaser continued.

mRNA-6231 is a lipid nanoparticle (LNP)-encapsulated mRNA-based therapeutic that encodes for mutein human interleukin 2, fused to human serum albumin, a Moderna spokesperson explained.

The company’s goal is the achieve more selectivity toward T regulatory cells. IL-2 and T-cell expansion may play a crucial role in restoring immune homeostasis.

Moderna has active clinic programs in five different therapeutic areas, including infectious disease, oncology, cardiovascular, rare disease, and autoimmune disease.

In April, Moderna announced that its mRNA vaccine candidate, mRNA-1647, at 50 micrograms, 100 micrograms, and 150 micrograms was generally well-tolerated in a Phase 2 study.

Neutralizing antibody geometric mean titers (GMTs) against epithelial cell infection were about 20-fold higher in CMV-seronegative participants after the third vaccination compared to the baseline GMT of the CMV-seropositive group.

Meanwhile, neutralizing antibodies GMTs against epithelial cell infection increased to at least 6.8 fold over baseline among CMV-positive participants after the third vaccination. 

Additionally, Moderna’s mRNA-1644 is a novel approach to HIV vaccine strategy in humans designed to elicit neutralizing HIV-1 antibodies (bNAbs). Currently, researchers are developing the strategy in collaboration with the International AIDS Vaccine Initiative (IAVI) and the Bill and Melinda Gates Foundation (BMGF). 

A Phase 1 study for mRNA-1644 will use human testing to validate the approach and antigens, and multiple novel antigens will target germline and immuno-focusing. 

To date, Moderna has entered 14 different mRNA vaccine candidates into clinical trials. Most notable is its mRNA-based vaccine for COVID-19. The company stated that it will invest resources and continue to leverage its mRNA platform to accelerate its mRNA vaccine pipeline.