A molecule that carries the recipe for making drugs inside body cells is exciting scientists and investors alike, attracting hundreds of millions of dollars in a scramble for the next promising area of biotechnology.
German and U.S. firms are leading the way in synthetic messenger RNA, or mRNA technology, a new approach to tackling a range of hard-to-treat diseases.
In theory, the promise of mRNA is enormous, ranging from cancer to infectious diseases to heart and kidney disorders, since it could be used to tackle the 80 percent of proteins that are difficult to affect with existing medicines.
Despite a recent sell-off in biotech stocks, sparked by U.S. Democratic Presidential candidate Hillary Clinton's threat to crack down on drug pricing, enthusiasm for mRNA is rising.
Today's biotech medicines use complex proteins or antibodies to treat disease, while traditional tablets such as aspirin or Viagra are simple chemicals. Harnessing synthetic mRNA is a different model altogether.
In effect, mRNA serves as software that can be injected into the body to instruct ribosomes, the "3D-printers" found inside cells, to churn out desired proteins.
"This is a radically different approach from conventional approaches, where therapeutic proteins are produced outside the human body and active ingredients need to be isolated, purified and cooled and then be inserted back into the human body at great complexity and cost," said CureVac co-founder and CEO Ingmar Hoerr.
Four-year-old Moderna Therapeutics, based in Massachusetts, which raised a record-breaking $450 million in a private funding round in January, valuing it at $3 billion, has so far hogged the limelight but German companies are flexing their muscles.
Privately-held CureVac in the university town of Tuebingen, which already has backing from Microsoft co-founder Bill Gates thanks to its vaccine work, last week raised $110 million from new investors, valuing it at $1.6 billion.
And Mainz-based BioNTech clinched a deal possibly worth up to $1.5 billion with Sanofi to use mRNA to fight cancer. BioNTech is owned by the Struengmann family who sold generic drugmaker Hexal to Novartis in 2005.
LONG-TERM BET
Single-stranded RNA, which helps to relay information encoded in double-helix DNA molecules, for a long time attracted only academic interest because it was seen as too unstable to handle.
But advances in chemistry have increased both stability and potency, paving the way to the creation of potential drugs, although big challenges remain to prove their clinical value.
"It's still a long-term bet," said Andy Smith, Chief Investment Officer at fund manager Mann Bioinvest. "I don't think it is ready for prime time just yet."
Still, ever more big pharmaceutical companies are lining up to do deals with mRNA firms.
Some of the most advanced work to date has been in vaccines, where CureVac is a leader with clinical trials in prostate cancer and rabies. Overall, the company has tested its products on more than 300 clinical trial participants and its relatively maturity means it could be the first mRNA player to go public.
The company says it is getting ready for a possible initial public offering, but declines to say when.
Moderna has yet to start clinical trials, although it has ambitious plans for parallel studies with multiple drug candidates, alongside partners including AstraZeneca, Merck & Co and Alexion.
Marcus Schindler, Vice President for Cardiovascular and Metabolic Drug Discovery at AstraZeneca, is particularly excited about the promise of mRNA in producing a radical new treatment for heart failure, by regenerating cardiac tissue.
AstraZeneca plans to start testing mRNA as an agent to improve coronary blood flow in human trials in 2016. This follows promising data in animals that suggests synthetic mRNA can be delivered accurately and produce the right amount of protein.
"The field is moving very rapidly," Schindler said. "I predict it will have a significant impact." As a chemically synthesized product, Schindler believes mRNA should be cheaper to make than current costly antibody drugs.
But potential obstacles remain in the form of optimizing drug delivery and possible side effects, while the history of biotech advances suggests some unforeseen setbacks are likely as the technology moves into large clinical trials.
Other companies working in the mRNA area include Argos Therapeutics, eTheRNA, Ethris and Factor Bioscience.
