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Messenger RNAs (mRNAs) work with DNA molecules to make our bodies function properly. They carry the genetic information stored in DNA and translate them into proteins, which help control cell division and metabolism. As a result, therapies that harness mRNAs can help combat a range of diseases.
mRNA vaccines became hugely popular in the race to develop a COVID-19 vaccine. They work by using a piece of mRNA, which instructs cells in the body to make a specific protein that is also present on the virus. When these proteins are made, the body’s immune system recognizes them as foreign and starts producing antibodies in response. This process effectively trains the immune system, preparing it to quickly recognize and fight the actual virus if it ever invades the body.
As mRNA technology evolves to prevent other infectious diseases, treat cancers and genetic disorders, more biotech companies have entered the field in recent times. Here are six mRNA companies that have recently raised funds to push their candidates into preclinical and clinical trials.
Table of contents
Abogen Biosciences
- Founded in 2019
- Location: China
- Lead candidate: ABO2011 in solid tumors
Based in the city of Shanghai, Chinese biotech company Abogen Biosciences uses its mRNA platform to create synthetic mRNA molecules, which are delivered with the help of a lipid nanoparticle (LNP) system.
LNPs not only aid in the targeted delivery of the mRNA into specific cells but also protect the mRNA molecule from degradation. Through dynamic precision mixing technology, non-toxic, pH-neutral LNPs are produced. This way, it allows for over a 90% encapsulation rate, which is the percentage of the drug that is successfully entrapped into a vector.
The focus of its pipeline is on cancer, infectious diseases, and rare diseases. Its mRNA-based COVID-19 vaccine targeting SARS-2-COV-2 Omicron is in phase 3 clinical trials, whereas the one targeting the SARS-COV-2 wild-type strain was granted Emergency Use Authorization (EUA) in Indonesia in 2022. This clearance was based on trial results that showed that the vaccine Awcorna had higher levels of neutralization and IgG antibodies against wild-type, Delta, and Omicron when compared to homologous boosters.
Its most advanced cancer therapy candidate is ABO2011, an mRNA-encoding human single-chain IL-12 protein to treat solid tumors. It is currently undergoing phase 2 trials.
Abogen’s series C financing round was deemed to be one of the largest private biotech funding rounds in China ever, according to a Fierce Biotech report. The company had raised $700 million back in 2021 to fuel its COVID-19 vaccine through the clinic.
Arcturus Therapeutics
- Founded in 2013
- Location: U.S.
- Lead candidates: LUNAR-OTC for OTC deficiency and LUNAR-CF for cystic fibrosis
Established in California, Arcturus Therapeutics is a late-stage mRNA company and is particularly a notable player in the mRNA vaccine space.
It has two platforms, Lunar and Starr. Lunar is a lipid-mediated nucleic acid delivery system that consists of a library of over 250 lipids. As for Starr, it combines Lunar with self-replicating RNA to create a nanoparticle delivery system to produce proteins in the body. The former is the system involved in the design of mRNA therapies, which has brought about LUNAR-OTC and LUNAR-CF, both of which are in phase 2 trials.
The candidate LUNAR-OTC is designed to treat a disease called ornithine transcarbamylase (OTC) deficiency, a genetic disorder that impairs the urea cycle in the body, leading to the toxic buildup of ammonia in the blood. As it is caused by a deficiency of the OTC enzyme, LUNAR-OTC directs the liver cells to produce the enzyme to prevent ammonia buildup. The inhaled mRNA is enclosed in fat molecules to aid its delivery.
On the other hand, LUNAR-CF, which is also an inhaled mRNA encased in tiny fat molecules, is delivered by a special nebulizer to address cystic fibrosis, a genetic disorder that causes mucus buildup in the lungs due to mutations in the CFTR gene. A normal copy of CFTR mRNA enters the lungs to prompt the production of CFTR and restore water and salt balance in the airways.
Meanwhile, Arcturus has several mRNA vaccines up its sleeve, one of which – the self-amplifying mRNA vaccine Kostaive – has been approved by the European Medicines Agency (EMA) for COVID-19. The development of Kostaive has been part of its long-standing partnership with Australian pharma giant CSL, with which it is conducting clinical and preclinical studies for other mRNA vaccine candidates to treat seasonal influenza and other infectious diseases.
Recently, Arcturus Therapeutics announced that it was doubling down on mRNA drug development after slashing early-stage vaccine programs in May. The last time it received funding was when it nabbed a $9 million grant from the Cystic Fibrosis Foundation two years ago.
Ethris
- Founded in 2009
- Location: Germany
- Lead candidate: ETH47 for asthma
Situated in Planegg in Germany, Ethris is devoted to using non-immunogenic messenger RNA (SNIM mRNA) to develop vaccines and therapies.
The company’s Stabilized Non-Immunogenic mRNA (SNIM RNA) platform generates stabilized non-immunogenic mRNA. This mRNA is said to overcome the instability of mRNA because of chemical changes in their structures. This can be used to create and replace proteins that can tame diseases.
It also has an LNP platform that allows efficient transport of mRNAs via inhalation to the lungs as well as via intramuscular injection for vaccination. Ethris evades the challenges of maintaining the quality of LNPs with the help of its lipidoid formulation and optimized nebulization technology.
Ethris’ ETH47 is in phase 2 trials for asthma and phase 1 trials for chronic obstructive pulmonary disease, both of which are chronic lung disorders that affect breathing. It encodes interferon lambda (IFNλ), a protein crucial for viral immunity in the airways. ETH47 is designed to target viral triggers of asthma exacerbations, one of the most common causes of acute symptoms in patients with asthma.
Also in its pipeline is ETH42 for a rare genetic disorder called primary ciliary dyskinesia (PCD). The condition is characterized by defects in the cilia, which are tiny hair-like structures that move mucus and particles out of the airways. By delivering mRNA that codes for the missing protein called CCDC40 that results in the condition to the lungs, it helps restore the proper function of the cilia. The candidate is currently in preclinical studies in three separate trials where it addresses three different targets in each trial.
To advance the development of ETH47, Ethris was awarded €10 million ($11.67 million) from EU4Health, the European Union’s largest health program in May.
Immorna
- Founded in 2019
- Location: China
- Lead candidate: JCXH-221 for COVID-19
Situated in North Carolina and Hangzhou, Immorna is focused on developing therapies made up of self-replicating RNA and mRNA.
Its mRNA pipeline is specialized in infectious diseases, the most advanced being JCXH-221 for COVID-19. It snagged investigational new drug (IND) clearance three years ago to begin phase 1/2 trials, which are ongoing. It is an LNP-based vaccine that targets SARS-CoV-2. Immorna’s LNPs are custom designed to deliver mRNA directly to cells.
Utilizing the natural translation mechanisms within the cell, the company’s mRNAs make the cell a biosynthetic factory for the target protein. This technology has also helped create the other mRNA drugs in the roster, including JCXH-105 for shingles, JCXH-107 for the flu, JCXH-108 for RSV, and JCXH-301 for Gaucher’s Disease, a rare, inherited metabolic disorder caused by fat buildup in certain organs because of an enzyme deficiency.
About a year ago, the company received a grant from the Bill & Melinda Gates Foundation to support the clinical development of its mRNA RSV vaccine. Prior to that, it bagged CN¥90 million ($12.64 million) in a series A round in 2023.
RNAimmune
- Founded in 2020
- Location: U.S.
- Lead candidates: RV-1730 for COVID-19 and RV-1770 for RSV
Located in Maryland, the startup RNAimmune has come up with its mRNA pipeline centered around treating cancer, infectious diseases, and rare diseases.
Two of its infectious disease candidates are in phase 1 trials, namely RV-1730 and RV-1770. The candidate RV-1730 is a COVID booster vaccine for SARS-CoV-2 and was granted IND status from the FDA two years ago. The vaccine encodes the Delta variant spike protein with the S6P mutation to enhance stability and immunogenicity.
The phase 1 study is investigating the safety and efficacy of the vaccine when it is administered as a single booster dose to people aged between 18 and 55 who have previously been vaccinated. The booster dosages are set at 15 µg, 30 µg, or 100 µg in three cohorts consisting of a total of 45 participants.
The other clinical candidate RV-1770 is being tested against the deadly respiratory syncytial virus (RSV). It was designed using artificial intelligence (AI). The vaccine has demonstrated immunogenic responses and neutralization against both type A and B strains of RSV in preclinical cotton rat studies.
Currently in the IND-enabling stages, the mRNA startup has vaccines targeting KRAS – a common mutated gene in cancers such as lung, skin, colon, and pancreatic cancers – and influenza.
It last secured $27 million in a series A funding round in 2022. The company is a subsidiary of Hong Kong- and U.S.-based Sirnaomics, which was set up in 2007.
Strand Therapeutics
- Founded in 2017
- Location: U.S.
- Lead candidates: STX-001 for solid tumors
American biotech company Strand Therapeutics programs mRNAs to target various kinds of proteins ranging from allosteric proteins, protein-protein complexes, and nucleic acid protein complexes to membrane proteins.
The mRNA constructs combine genes for self-replication derived from RNA viruses that are genetically programmed. Once they enter target cells, they translate the therapeutic protein they are encoding to treat the disease in the specific cells. And if they go into the wrong cells, they are degraded by those cells.
Committed to creating mRNA-based drugs, the company’s most advanced drug targets IL-12 and is used to treat melanoma, triple-negative breast cancer (TNBC), and other solid tumors. Its mRNA therapy STX-001 obtained IND clearance to embark on its clinical journey to address solid tumors last year.
The Massachusetts-based startup pocketed $153 million in a series B funding round to move its pipeline forward two months ago.
mRNA therapeutics: heyday not over
mRNA therapeutics gained prominence for their ability to limit COVID-19 infections, but it hasn’t ended there. Apart from their growing use in infectious disease vaccines, they are being trialed as cancer vaccines, as seen with Abogen Biosciences and RNAimmune, among others. The biggest news in the field this year was German multinational company BioNTech’s $1.25 billion acquisition of fellow German mRNA therapeutics developer CureVac. The two have been major players in the space and are among the pioneers of mRNA-based cancer vaccines.
Meanwhile, biotechs are employing mRNA in their cell therapy platforms. Companies like Massachusetts-based Intellia Therapeutics and Tessera Therapeutics use mRNA as a component in their CRISPR/Cas9 LNP delivery system for their gene editing programs. As mRNA research grows, it has also diversified, and its ability to be integrated into other drug delivery systems has been recognized.
This article was originally written by Roohi Mariam Peter in April 2024 and has since been updated.
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