New York September 25 2021: The global success of messenger RNA-based COVID-19 vaccines has given added momentum to early-stage trials of similar technology to treat other diseases.
In August, Sanofi purchased U.S. biotech Translate Bio Inc., which specializes in mRNA-based technology used in Pfizer Inc.-BioNTech SE's and Moderna Inc.'s COVID-19 vaccines, for $3.2 billion as the French company looked to beef up its own vaccine portfolio. Other pharmaceutical giants, like Merck & Co. Inc. and Gilead Sciences Inc., have also shown interest in researching how mRNA can be used for indications beyond COVID-19, from cancer to liver disease and respiratory infections.
Many of these mRNA vaccines and therapies are still in the early phases of clinical testing, but companies believe they have the potential to result in first-in-class treatments. Translate Bio's MRT5005, for instance, is an inhaled mRNA therapeutic in phase 1/2 trials for patients with cystic fibrosis, a genetic disease that causes frequent lung infections.
Results from a second interim analysis of the trial data in March found that while repeat dosing of MRT5005 was generally safe and well-tolerated, there was no pattern of increases in ppFEV1, a measure of lung functionality. Despite this setback, the company said it is continuing to pursue innovative mRNA products for cystic fibrosis.
"We have seen the impact that mRNA is having across the vaccine landscape, and given the novelty of its science, I am hopeful that mRNA may have a similar role in treating pulmonary diseases including cystic fibrosis," Steven Rowe, director of the Gregory Fleming James Cystic Fibrosis Research Center and the trial's principal investigator, said in a March 17 statement.
San Diego, Calif.-based Arcturus Therapeutics Holdings Inc. is another biotech utilizing mRNA to combat a genetic disorder. Ornithine transcarbamylase, or OTC, deficiency is a rare condition characterized by a lack of the OTC enzyme, which usually breaks down and removes nitrogen in the body. This can cause high levels of ammonia in patients' blood, leading to coma, seizures or death.
Arcturus' therapy ARCT-810 is an intravenous solution in phase 1b testing with an estimated primary completion in November. In preclinical studies, researchers found that the company's Lunar platform could deliver OTC mRNA to liver cells in mice with the deficiency, improving their OTC levels.
The company — which also has its own inhaled mRNA therapy for cystic fibrosis in preclinical development — is recruiting for a phase 2 multi-dose trial of ARCT-810 in the U.K., Arcturus told S&P Global Market Intelligence.
BioNTech, which co-developed the first COVID-19 vaccine to receive emergency authorization in the U.S. with Pfizer, has a portfolio of 19 other mRNA vaccines and therapies in various stages of development, including several in early-stage trials for types of cancer, according to the company's website.
One of these vaccines is BNT112, which is being studied to treat patients with two types of prostate cancer. The vaccine uses BioNTech's FixVac technology, which targets antigens that the company has identified in patients with a specific type of cancer. The lead candidate for this technology is BNT111, which is in a phase 2 trial for an advanced form of skin cancer.
Another of the company's therapies is BNT131, a collaboration with Sanofi that is in early-stage testing as a way to help the immune system more easily recognize and fight off solid cancer tumors. BNT131 uses the company's ITIT technology, which involves injecting cytokine-encoding mRNA directly into the tumor in order to avoid the toxicities that can be caused by systemic cancer treatments. Cytokines are proteins that play a key role in controlling the growth and activity of other immune system cells and blood cells.
Meanwhile, fellow mRNA COVID-19 vaccine maker Moderna is collaborating with Merck & Co. Inc. to explore whether Moderna's personalized cancer vaccine candidate mRNA-4157 can be used in combination with Merck's blockbuster cancer drug Keytruda to improve patients' outcomes. MRNA-4157 is in phase 1 trials for patients with resected solid tumors and alongside Keytruda in patients with tumors that cannot be resected.
Autoimmune and infectious diseases
Away from cancer, BioNTech has set its sights on lower-income countries, notably in Africa, as some of the biggest potential beneficiaries of the German company's malaria mRNA program.
"We believe the technology behind [the] COVID-19 vaccine has the potential against a range of other infectious diseases as well as the potential to play an important role in future pandemic preparedness programs," CEO Uğur Şahin said on an Aug. 9 earnings call. "We aim to develop the first mRNA vaccines with durable protected immunity for prevention of malaria with the initiation of a clinical path by the end of 2022."
Autoimmune disorders have been another popular area for mRNA experimentation. Moderna announced Aug. 2 it had dosed its first patient in a phase 1 trial of mRNA-6231, a therapeutic modified for the expansion of regulatory T cells. Regulatory T cells help suppress immune responses of other cells and can prevent autoimmune diseases.
Moderna has also begun testing an mRNA vaccine targeting multiple strains of seasonal influenza, and plans to explore potential combination vaccines against flu, COVID-19, respiratory syncytial virus and human metapneumovirus.
"Our vision is to develop an mRNA combination vaccine so that people can get one shot each fall for high efficacy protection against the most problematic respiratory viruses," CEO Stéphane Bancel said in a July 7 statement.
In June, Sanofi's vaccines unit and Translate Bio began a phase 1 trial of an mRNA flu vaccine targeting the A/H3N2 strain of the virus specifically.
"The first clinical trial of a seasonal mRNA flu vaccine candidate is an exciting milestone in our quest for the next generation of influenza vaccines," Jean-François Toussaint, global head of research and development at Sanofi Pasteur, said in a statement. "We've all witnessed the promise of mRNA technology during this pandemic and are now looking to extend that promise to select annual vaccines."