The mRNA Revolution
With the pandemic, mRNA has moved from a very technical term to something that virtually everybody knows. This a revolution for a technology first theorized in the 1970s. mRNA links the blueprint (DNA) and the functional tool in cells (proteins).
Because of these vaccines, the public has now associated mRNA molecules with vaccination and immunity, but this is far from the only possible application.
The key is to synthesize artificially, in massive amounts, and at low-cost mRNA. The other important idea is that it essentially allows us to manipulate the genetic code almost as easily as computer code. So, we could reprogram biology in a similar way we program the digital world.
The Next Big Thing For mRNA: Cancer Therapies
Beyond specific pathogens, old like HIV or new like COVID, another major cause of mortality in the developed world is cancer. The main difficulty in treating cancer is that it is not just one disease. It is more of a thousand different possible dysfunctions of the body's cells. So, it would ideally need a customized solution for each type of cancer. Or maybe even for every single cancer in each patient.
The only way to do so is to use a fully programmable treatment that can be fined tuned to each cancer specificity. Something that only 2 technologies can achieve currently: gene therapy/gene editing and mRNA.
How To Invest Cancer mRNA Therapies
One of the leading companies in mRNA cancer therapies is BioNTech, which is building from its success in developing the mRNA vaccine commercialized by Pfizer. BioNTech currently has 12 different candidates in cancer treatments, covering cancer in the ovaries, prostate, intestines, skin, head, neck, and multiple solid tumors. Most are on phase I clinical trials, with already 3 candidates in phase II. They are either fully owned or in partnership with Sanofi and Genentech.
Moderna is working on mRNA treatment for lymphoma and solid tumors both in phase I clinical trials.
Curevac is working on CV8102, an RNA treatment for carcinoma that is still in pre-clinical development.
The Next mRNA Technologies
This article wanted to focus on the most promising technology. But it was hard to pick just one. We went for the one with both the largest possible impact and the most innovative. So cancer, with its very large number of affected people, was the top choice. Still, some other applications should also be given an honorable mention.
Obviously, after the commercial success of the Covid-19 vaccine, any other pathogenic disease could be the target of new mRNA vaccines. This includes older vaccines. For example, Moderna is working on an mRNA vaccine for the flu. Moderna is also working on diseases that do not have vaccines currently and is working on RSV, zika, HIV, Epstein-Barr virus, or cytomegalovirus. The technology could equally be used for malaria and other poorly treated diseases in poor countries.
BioNTech (BNTX) is also working on mRNA vaccines for shingles, tuberculosis, malaria, HIV, and herpex virus.
Curevac (CVAC) is also working on mRNA vaccines for Lassa yellow fever, RSV, rabies, malaria, and rotavirus.
Together with gene editing, the treatment for rare diseases is progressing greatly thanks to mRNA promises.
Moderna is working on 7 genetic diseases, including cystic fibrosis and phenylketonuria.
The mRNA profile of cancer cells is different from that of healthy cells. For example, researchers have found differences in 13mRNA and 29 other types of RNA for a type of liver cancer. Leveraging our knowledge will allow for more precise diagnostics, including through just a blood sample.
This is commonly referred to as “liquid biopsy,” leveraging Next-Generation-Sequencing, a field in which Illumina (ILMN) is at the forefront through its Grail subsidy (we covered Illumina in detail in this article comparing it to its competitor PacBio). Such diagnostic tools will allow for early cancer detection, dramatically increasing the survival rate.
Researchers at Penn Medicine are using mRNA to modify liver genes and reduce heart attack risks. They are also working on a cure for fibrosis in the heart tissues, a major cause of heart failure.
The leaders in future mRNA applications are the same companies that have made the mRNA vaccine revolution happen. They are all down from their 2021 peak when markets were obsessed with deploying Covid-19 vaccines. This might be extremely short-sighted, as mRNA has only barely begun to change the way medicine is practiced.
Regarding mRNA cancer treatment, BioNTech seems to have an advantage, with more candidates in clinical trials than Moderna and Curevac together.
Moderna and BioNTech are on equal footing with other non-Covid-related vaccines, with Moderna having an advantage in rare genetic diseases.
Curevac is by all means smaller and lagging behind its two larger competitors. But it is also trading at a 15x-30x lower valuation.
Investors interested in the largest possible upside might want a second look at Curevac, as it has by far the smallest valuation of the 3 leaders in mRNA technology despite candidates in cancer treatments and vaccines.
Moderna will likely get results in the orphan disease segment, a profitable market per treatment but with few patients. So, a lot of its future revenues are likely to come from new vaccines.
mRNA cancer treatments are riskier as they are less proven than gene therapies for genetic diseases. They also have a larger potential upside if the therapeutic results are good. So, while riskier, they might also provide a significant upside for BioNTech over its competitors.