A lipid-encapsulated mRNA encoding a potently neutralizing human monoclonal antibody protects against chikungunya infection. - Moderna, Preclinical Publication

A lipid-encapsulated mRNA encoding a potently neutralizing human monoclonal antibody protects against chikungunya infection

Moderna Announces Publication of Preclinical Data for Chikungunya Antibody Program
Published in Science Immunology, study shows mRNA encoding antibody against chikungunya virus is well tolerated, results in linear dose-dependent protein expression and provides 100 percent protection against infection in animals

Cambridge, Mass., based Moderna is a well connected entity in the biopharma industry. The company has strategic partnerships with AstraZeneca, Plc. and Merck, Inc., as well as the Defense Advanced Research Projects Agency (DARPA), an agency of the U.S. Department of Defense; the Biomedical Advanced Research and Development Authority (BARDA), a division of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS) for development programs.
Chikungunya is an infection caused by the chikungunya virus (CHIKV). The infection symptoms include fever and joint pain, other results of an infection, may include headache, muscle pain, joint swelling, and a rash. These typically occur two to twelve days after exposure. Symptoms usually improve within a week; however, occasionally the joint pain may last for months.[2] The risk of death is around 1 in 1,000 and that is mostly the very young, old, and those with other health problems are at risk.
Two types of mosquitos: Aedes albopictus and Aedes aegypti distribute the virus between people. These mosquitoes mainly bite during the day. In addition to people, the virus may circulate within a number of animals including birds and rodents. Diagnosis is usually done by either testing the blood for the virus's RNA or the presence of antibodies to the virus. The symptoms can be mistaken for those of dengue fever and Zika fever. After a single infection it is believed most people become immune.


“These preclinical data demonstrate three critical features of our therapeutic platform: first, that it was well-tolerated, with no dose-limiting toxicities; second, we showed linear dose-dependent pharmacology; and third, that the expressed protein was able to prevent disease,The mRNA and delivery technologies presented here underpin our expansion into systemic therapeutics in humans, first with mRNA-1944 against chikungunya virus this past January, and soon with our first metabolic rare disease program, mRNA-3704, for methylmalonic acidemia.” said Stephen Hoge, M.D., president at Moderna.

James Crowe Jr., MD, director of the Vanderbilt Vaccine Center, said "Using the body’s own machinery to produce antibodies against chikungunya by using mRNA may be a powerful way to combat the virus, We are pleased that our early work contributed to these preclinical findings and look forward to the results from the ongoing Phase 1 clinical study of the antibody against chikungunya virus.”

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Moderna, Inc., (Nasdaq: MRNA) a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, today announced the publication of preclinical data in Science Immunology, showing that mRNA encoding a human monoclonal antibody against the chikungunya virus delivered in a proprietary lipid nanoparticle (LNP) can protect from infection by the virus in vivo. These data supported the initiation of a Phase 1 program of mRNA-1944 against chikungunya virus in January 2019 to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of escalating doses of mRNA-1944 via intravenous infusion in healthy adults.
“These preclinical data demonstrate three critical features of our therapeutic platform: first, that it was well-tolerated, with no dose-limiting toxicities; second, we showed linear dose-dependent pharmacology; and third, that the expressed protein was able to prevent disease,” said Stephen Hoge, M.D., president at Moderna. “The mRNA and delivery technologies presented here underpin our expansion into systemic therapeutics in humans, first with mRNA-1944 against chikungunya virus this past January, and soon with our first metabolic rare disease program, mRNA-3704, for methylmalonic acidemia.”

The preclinical data published today showed that treatment with mRNA was well tolerated at doses ranging from 0.3 mg/kg to 3.0 mg/kg in non-human primates, with linear dose-dependent pharmacology, meaning that increases in mRNA doses result in predictable and proportionate increases in expressed antibody in the blood. Finally, in a mouse viral challenge model for chikungunya virus infection, the mRNA-encoded protein provided protection from arthritis, musculoskeletal tissue infection and death. Extrapolating these findings from the preclinical models suggests that persistence of antibody levels of at least 1 microgram per milliliter could be protective against chikungunya virus infection in humans.

“Using the body’s own machinery to produce antibodies against chikungunya by using mRNA may be a powerful way to combat the virus,” said James Crowe Jr., MD, director of the Vanderbilt Vaccine Center. “We are pleased that our early work contributed to these preclinical findings and look forward to the results from the ongoing Phase 1 clinical study of the antibody against 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, a mosquito-borne virus. 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. 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, and the antibody was initially identified by researchers at Vanderbilt University Medical Center.

A link to the publication, A Lipid-encapsulated mRNA Encoding a Potently Neutralizing Human Monoclonal Antibody Protects Against Chikungunya Infection (Kose, et al.), can be found here.

Moderna currently has 21 mRNA development candidates in its portfolio spanning infectious diseases, immuno-oncology, rare diseases and cardiovascular disease, with 11 of these development candidates now in the clinic. The Company’s pipeline can be found at www.modernatx.com/pipeline. In the past three years, Moderna and collaborators have published more than 26 peer-reviewed papers, with 13 in the last year alone.

About Chikungunya

Chikungunya is a mosquito-borne virus that poses a significant public health problem in tropical and subtropical regions. The disease is characterized by an acute onset of fever, rash, muscle pain, and sometimes debilitating pain in multiple joints. There are currently no effective therapies or approved vaccines to treat or prevent chikungunya infection or disease, and effective mosquito control is challenging. Currently, people infected with chikungunya are treated with non-steroidal anti-inflammatory drugs to relieve some symptoms. In addition to a systemic secreted antibody that could provide passive immunity, Moderna is also exploring using mRNA to encode viral antigens as a prophylactic vaccine against the chikungunya virus (mRNA-1388).

About Moderna

Moderna is advancing messenger RNA (mRNA) science to create a new class of transformative medicines for patients. mRNA medicines are designed to direct the body’s cells to produce intracellular, membrane or secreted proteins that can have a therapeutic or preventive benefit and have the potential to address a broad spectrum of diseases. Moderna’s platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, providing the Company the capability to pursue in parallel a robust pipeline of new development candidates. Moderna is developing therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and cardiovascular diseases, independently and with strategic collaborators.

Headquartered in Cambridge, Mass., Moderna currently has strategic alliances for development programs with AstraZeneca, Plc. and Merck, Inc., as well as the Defense Advanced Research Projects Agency (DARPA), an agency of the U.S. Department of Defense; the Biomedical Advanced Research and Development Authority (BARDA), a division of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS). Moderna has been ranked in the top ten of Science’s list of top biopharma industry employers for the past four years. To learn more, visit www.modernatx.com.


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