Messenger RNA, magic potion or new medical eldorado?

While Covid contaminations are on the rise again in France and a first easy-to-take drug could reduce the risk of hospitalization by two, the health technology market remains very lively. The first 100% biotech billionaires have appeared among the very wealthy, and investors are scrutinizing biomedical technologies more than ever. Who are the new rich doped by the anti-Covid vaccine, how does the biotechnology market work, is the mRNA platform a new El Dorado? Our three-part series on the new post-Covid healthcare billionaires.

___

While the 2021 Nobel Prize in Medicine has just eluded two key scientists in the use of this technology, messenger RNA (mRNA) remains very much in view. Researchers are concentrating on this technology, big pharmas are buying up biotechs whose specialty it is at exorbitant prices, while investors are crazy about this research. With the success of the BioNTech and Moderna vaccines, we are witnessing a veritable “mRNA-ania”!

Even if Sanofi abandoned the development of its messenger RNA vaccine against Covid-19 on September 28, 2021, considered too late compared to its competitors, big pharma is now relying on this technology against other viruses. In the spring, he got his hands on the specialized biotech mRNA Tidal Therapeutics before acquiring all the shares of the American company Translate Bio for 2.7 billion euros. Since the success of the agreement between Pfizer and BioNTech around the anti-Covid vaccine, other big pharma / biotech partnerships are in the pipeline, such as the one concluded between GSK and the German biotech CureVac.

For investors, mRNA biotechs have become promising nuggets. Everyone dreams of discovering a future Moderna before the hour of success. The market capitalization of the five listed companies focused on mRNA platforms has multiplied by 20 in eighteen months, from 15 billion dollars at the end of 2019 to 300 billion last August. BioNTech's rose to $50 billion and Moderna's reached $126 billion.

150 mRNA drug candidates in the making

In fact, pharma in mRNA mode could give rise to real medical advances. There are already more than 150 projects underway: vaccines, treatments against cancer, against genetic or autoimmune diseases, etc. This mRNA technology uses genetic medicine to protect or treat us, but without interfering with the DNA of our cells, unlike gene therapy. Messenger RNA is a "ribonucleic" acid molecule. In our cells, this acid recovers the instructions of the DNA written in the form of biological code (the famous 4 letters: A + C + G and U). It thus plays the role of the "order form" to indicate to the production centers of our cells the code of the proteins to be manufactured. In this way, these centers provide the proteins that our body needs to function. And the useful elements to treat us when the order form is an injected mRNA. mRNA medicine injects a whole acid, or just a small part of the instructions that will add to those of the natural mRNA to produce more or less of the desired protein.

50 years to reach the market

mRNA was discovered by François Jacob and François Gros in 1961 at the Institut Pasteur. Although the first results of trials in the late 1990s were encouraging, the market for medical innovations was then captivated by the potential of gene therapies: the correction of faulty genes to cure genetic diseases. In 2000, mRNA technology also suffered from technological problems. Leading a research group on RNA, Maria Duca, CNRS researcher at the Nice Institute of Chemistry (University of the Côte d'Azur) recalls the stages:

@cashleyg Like truly don't understand how mainly just a meat and fat diet is supposed to be good, like so many peop… https://t.co/AulvNEIvga

— cari Mon Aug 24 06:19:03 +0000 2020

In 2005, the first obstacle was removed with protection that did not cause excessive inflammation. An invention developed by Hungarian researcher Katalin Kariko, one of the two RNA inventors tipped for the 2021 Nobel Prize in Medicine. The other challenge, bio-distribution, has also been met. With BioNTech's nanoparticle for the covid vaccine, the serum manages to activate the immune system. From these solutions, the first mRNA vaccines were designed against the Ebola virus from 2015, before the highly anticipated one against Covid.

Leads for medical advances

With more capital to develop projects, mRNA could now allow great medical advances. Professor at the University of Orléans and researcher at the CNRS Molecular Biophysics Center, Chantal Pichon is a pioneer of this technology.

Three ways to treat with mRNA

The mRNA projects are mainly developed on three models of medical activity: prophylactic vaccines, therapeutic vaccines, and treatments for cancers, genetic or autoimmune diseases.. .

Prophylactic RNA mRNA vaccines are the first on the market, they are those that protect patients from infectious diseases such as Covid or Ebola fever. For these vaccines, RNA technology has the advantage of reducing research and development (R&D) times. Once the target has been identified to create antibodies against the virus, all you have to do is program the machine to synthesize. Still on this principle, we can also quickly adapt these vaccines to new variants. According to the journal Nature, “the average maximum pipeline revenue per asset for prophylactic mRNA vaccines will be approximately $800 million globally (for products other than Covid-19 vaccines).” Already, Moderna has just launched an HIV vaccine in a phase 1 clinical trial, while Sanofi is developing its next flu vaccine in mRNA format.

Therapeutic vaccines are a form of cancer immunotherapy treatment. Using the same principle, they direct the immune system to the cancerous tumors to be destroyed, depending on the genetic mutations of the disease. Advantage: these treatments can attack cancers that are usually difficult to treat and offer new strategies. Laboratories are also developing therapeutic vaccines that attack different mutations in multiple tumours. These products will arrive on the market by 2035, and the journal Nature estimates the market between 7 and 10 billion dollars for this first year.

Finally, mRNA medicine develops therapeutic treatments against cancer, pain, kidney failure, neurological, infectious, genetic, metabolic, cardiovascular, gastrointestinal, respiratory, immunological and dermatological diseases. With or around mRNA. Palma Rocchi, Inserm research director at the Cancer Research Center of Marseille (CRCM), is developing a start-up to treat prostate cancer, with what are called "antisense oligonucleotides".

These elements are another strategy that modify the mRNA of our cells giving them new instructions. “They correct the instructions issued by cancer-causing genes. They can trigger normal production of a protein that the body has failed due to disease. They can also block the production of another protein that is harmful to the patient. Since 2013, the United States has marketed various antisense oligonucleotide treatments, including familial hypercholesterolemia (Kynamro), spinal muscular atrophy (Spinraza) or Duchenne dystrophy (Exondys 51). One of the advantages of this RNA medicine is a very rapid marketing due to the ease of production of the molecules. »

According to the journal Nature, therapeutics will be an opportunistic area for mRNA-based products, with many indications. But it is still difficult to say to date that these treatments will have a clinical advantage over gene therapy or recombinant proteins. These solutions will also have to refine their bio-distribution capabilities.

While waiting for all these medical innovations, this “mRNA-ania” is clearly boosting the biotech sector. More and more of them are entering the stock market under the effect of the planetary successes of BioNTech and Moderna.

8 mins

Share: