Moderna has announced the dosing of the first subject in a phase 1 clinical trial evaluating the safety and tolerability of escalating doses of mRNA-1944 via intravenous infusion in healthy adults.
This is the first monoclonal antibody encoded by mRNA to be dosed in a human and the first development candidate from the Company’s systemic therapeutics modalities to start clinical testing.
We believe this trial will give us important information about how mRNA may be used to make systemically-available complex therapeutic proteins in a consistent, dose-dependent fashion,” said Tal Zaks, M.D., Ph.D., chief medical officer at Moderna. “Dosing the first monoclonal antibody encoded by mRNA in humans is a significant milestone for our team and mRNA platform. We look forward to learning about the functionality of our mRNA-encoded antibody in neutralizing the Chikungunya virus.”
mRNA-1944 encodes a fully human IgG antibody originally isolated from B cells of a patient with a prior history of potent immunity against Chikungunya infection. It is composed of two mRNAs that encode the heavy and light chains of this anti-Chikungunya antibody within Moderna’s proprietary lipid nanoparticle (LNP) technology. Preclinical studies of mRNA-1944 showed linear dose-dependence, meaning increases in the dose of mRNA led to nearly proportionate increases in antibody production.
The research and development of mRNA-1944 was financially supported by the Defense Advanced Research Projects Agency (DARPA), an agency of the U.S. Department of Defense.
The randomized, placebo-controlled Phase 1 study is designed to evaluate the safety and tolerability of up to four ascending dose levels (0.1, 0.3, 0.6, 1 mg/kg cohorts with 8 subjects per cohort) of mRNA-1944 in healthy adults, administered via intravenous infusion.
Other objectives are to determine pharmacodynamics in the form of serum antibody expression and whether the antibodies produced against the Chikungunya virus are sufficiently active to neutralize viral infection in vitro.
Moderna has 21 mRNA development candidates in its pipeline, with 12 programs now in clinical development. These investigational medicines are grouped together into six modalities based on similar mRNA technologies, delivery technologies and manufacturing processes.
Typically, programs within a modality will also share similar pharmacology profiles, including the desired dose response, the expected dosing regimen, the target tissue for protein expression, safety and tolerability goals as well as their pharmaceutical properties.
Moderna scientists designed the Company’s systemic secreted therapeutics modality to achieve a therapeutic effect in one or more tissues or cell types by increasing levels of desired secreted proteins outside the cell, either in circulation or in contact with the extracellular environment.
The goal of this modality is to provide secreted proteins, such as antibodies or enzyme replacement therapies across a wide range of diseases, such as infectious diseases and rare genetic diseases. Three development candidates are currently included in this modality: antibody against Chikungunya virus (mRNA-1944 in a Phase 1 study); Relaxin (AZD7970 in IND-enabling GLP toxicology studies); and Fabry disease (mRNA-3630 in IND-enabling GLP toxicology studies).
The systemic intracellular therapeutics modality uses the same delivery technology and was designed to achieve a therapeutic effect in one or more tissues or cell types by producing proteins encoded by mRNA inside the cell, either located in the cytosol or specific organelles, like the mitochondria. The goal of this modality is to provide intracellular proteins, such as intracellular enzymes and organelle-specific proteins, as safe, tolerable and efficacious therapies.
Moderna currently has three programs in this modality focused on rare genetic diseases that cannot be addressed using recombinant proteins. These include methylmalonic academia or MMA (mRNA-3704 with an open IND for a Phase 1/2 study); Propionic Acidemia or PA (mRNA-3927 in IND-enabling GLP toxicology studies); and Phenylketonuria or PKU (mRNA-3283 in IND-enabling GLP toxicology studies).
Source: Company Press Release