With the launch of the clincial trial for mRNA-6231, the company’s mRNA-encoded IL-2 modified for the expansion of regulatory T cells, the company now has active clinic programs in five different therapeutic areas: infectious disease, oncology, cardiovascular, rare disease and autoimmune disease.
mRNA‑6231 is a lipid nanoparticle (LNP)‑encapsulated mRNA-based therapeutic that encodes for mutein human interleukin 2, fused to human serum albumin (HSA‑IL2m), with the goal of achieving enhanced selectivity toward T regulatory cells. IL-2 through preferential expansion of Tregs is hypothesized to play a central role in restoring immune homeostasis.
The trial is a Phase 1, first‑in‑human, dose‑escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of mRNA‑6231 in healthy adult participants (between 18 and 50 years of age), following subcutaneous administration of a single dose of mRNA‑6231.
“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,” said Ruchira Glaser, MD, Sr. Vice President and Therapeutic Area Head, Rare Disease, Autoimmune & Cardiovascular.
“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.”
Potential in therapeutics
Moderna’s headline work has been in mRNA vaccines, developing its COVID-19 vaccine and taking flu and HIV vaccine candidates into the clinic this year, among other programs.
While it aims to ‘build what could be the best vaccine company’, it also set out its ambitions during its Annual Vaccines Day in April to ‘transform medicine… again… with mRNA therapeutics’.
Whereas 2020 was the year of COVID-19 vaccine development, it said 2021 could be the year of proof-in-concept in therapeutics: with seven clinical proof-of-concept trials.
In January last year, it announced its expansion into the autoimmune therapeutic area with two autoimmune candidates in IND-enabling studies, which share the same LNP as its Chikungunya antibody program.
These are PD-L1 / mRNA-6981, with the first indication intended to be autoimmune hepatitis; and IL-2 / mRNA-6231, with IL-2 based therapeutics being evaluated for a wide range of autoimmune conditions.
Moderna's autoimmune therapeutic area
Autoimmune diseases are characterized by immune activation in response to antigens normally present in the body, reflecting a loss of tolerance. Within this therapeutic area, the Company is developing two potential medicines, mRNA-6231 and mRNA-6981, designed to engage peripheral tolerance pathways to dampen autoimmune activation and help restore immune homeostasis, thereby reducing autoimmune pathology.
mRNA-6231 is an mRNA encoding for a long-acting IL-2 mutein designed to preferentially activate and expand the regulatory T cell population, dampening the immune response.
mRNA-6981 is an mRNA encoding for PD-L1 and is designed to augment cell surface levels of PD-L1 on myeloid cells, providing co-inhibitory signals to self-reactive lymphocytes.