mRNA-1944 / Moderna - LARVOL DELTA

Application of Allometric Scaling and Translational Modeling to Predict Human Pharmacokinetics of mRNA-Encoded Antibodies. (PubMed, Mol Pharm) - "We developed an allometric scaling framework for human pharmacokinetic (PK) prediction of antibodies expressed from intravenously administered mRNA-LNPs, leveraging preclinical and clinical data for BNT141 (encoding RiboMab01, a full IgG1) and BNT142 (encoding RiboMab02.1, a bispecific Fab-scFv-based T-cell engager)...A mechanistic cross-species translational model was further developed that integrated mRNA-specific elimination and translation efficiency parameters to characterize the exposure of the translated antibodies from mRNA-based therapeutics...Validation with publicly available mRNA-1944 (encoding CHKV-24, full IgG1) data confirmed both the allometric scaling and translational modeling methods' robustness when scaling from NHP data. Taken together, these results support a generalized cross-species PK relationship that is independent of the molecular characteristics of the translated antibodies or antibody-like protein products. This integrated scaling and..."

First-in-human • Journal • PK/PD data • AVEN

mRNA-Encoded Antibodies: An Emerging Paradigm in Antiviral Protection. (PubMed, Biomolecules) - "Finally, we discuss the translation of this platform toward clinical application, highlighted by the completion of Phase I evaluation of Moderna mRNA-1944 against chikungunya virus. Together, these studies position mRNA-encoded antibodies as a flexible and rapidly deployable platform for passive immunization against emerging viral threats."

Journal • Review • Chikungunya • Infectious Disease

Differences and Similarities of the Intravenously Administered Lipid Nanoparticles in Three Clinical Trials: Potential Linkage between Lipid Nanoparticles and Extracellular Vesicles. (PubMed, Mol Pharm) - "Here, we reviewed three clinically tested intravenously administered LNPs (patisiran, mRNA-1944, and NTLA-2001). We further summarize the basics of extracellular vesicles (EVs) and discuss the potential linkages between LNPs and EVs. This Review provides an understanding of the human clinical data of intravenous LNP formulations, which can be potentially explored to develop next-generation LNP-and EV-based drug delivery carriers."

Journal • Review • Infectious Disease • Novel Coronavirus Disease

A phase 1 trial of lipid-encapsulated mRNA encoding a monoclonal antibody with neutralizing activity against Chikungunya virus. (PubMed, Nat Med) - P1 | "To our knowledge, mRNA-1944 is the first mRNA-encoded monoclonal antibody showing in vivo expression and detectable ex vivo neutralizing activity in a clinical trial and may offer a treatment option for CHIKV infection. Further evaluation of the potential therapeutic use of mRNA-1944 in clinical trials for the treatment of CHIKV infection is warranted."

Journal • P1 data • Chikungunya • Immunology • Infectious Disease • Musculoskeletal Pain • Rheumatology • IGH

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of mRNA-1944 in Healthy Adults (clinicaltrials.gov) - P1; N=39; Completed; Sponsor: ModernaTX, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Chikungunya • Infectious Disease

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of mRNA-1944 in Healthy Adults (clinicaltrials.gov) - P1; N=39; Active, not recruiting; Sponsor: ModernaTX, Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Sep 2020 ➔ Jun 2021; Trial primary completion date: Sep 2020 ➔ Jun 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Chikungunya • Infectious Disease