Moderna to Use mRNA Technology Against Flu, HIV, and Cancer

Moderna, the Cambridge, Massachusetts based biotechnology firm, has had a remarkable year, rising from obscurity to giving the world the second vaccine against the coronavirus; now it will weaponize the same mRNA technology against HIV, cancer and other maladies that plague mankind.

The upstart pharmaceuticals developer has also reached a $100 billion market cap as a result of their nearly round-the-clock efforts in developing their mRNA-based coronavirus vaccine. But it seems this only set the scene for even more monumental challenges in the future, as the firm turns its focus toward one of the great scourges of mankind, cancer, as well as HIV, the Zika Virus, and influenza.

As of one year ago, Moderna had exactly zero marketed products using a completely  unproven technology. Nothing it had ever produced had completed a large-scale clinical trial.

The new mRNA vaccines deliver a genetic code, informing cells how to make the virus proteins that provoke an immune response to Covid-19; from that point onward, our own bodies’ cells take on that mission.

Moderna will soon “Totally disrupt the vaccine market”

Needless to say, how its new mRNA-based coronavirus vaccine would fare in actual trials and real-world use was a giant unknown in an ultra competitive pharmaceuticals industry.

Now, the Massachusetts firm expects to produce its 1 billionth dose of its coronavirus inoculation and earn a staggering $19 billion in revenue.

Incredibly, the company has not been absorbed into another, larger firm — meaning its profits are all its own. Now, its market value, reaching $100 billion on July 14th of this year, is greater than the behemoth Bayer AG, and even biotech pioneer Biogen Inc., which was founded thirty years ago.

The speed with which Moderna and its primary mRNA competitor, a partnership between Pfizer Inc. and BioNTech SE, devised their shots has made a major contribution to the fight to end the pandemic.

The Moderna success story came as a breath of fresh air in 2020, at a time when the coronavirus ran rampant around the world and many firms had scientists devoting around the clock efforts to finding a vaccine or cure for the virus.

While health officials are taking heed of a rare but very treatable heart inflammation that has occurred in teenagers and young adults who receive the vaccine, the inoculations that use mRNA technology have reigned supreme, the countries around the world ordering as many doses as they are allowed to or have the funds to buy.

Moderna Chief Executive Officer Stéphane Bancel has stated from the outset that developing and manufacturing a coronavirus vaccine will serve as an opening volley in the long game of finding new treatments for other maladies that have long plagued mankind.

He takes the position that if mRNA did indeed work, it will serve as the basis of an entire new industry that will be aimed at treating or curing not only the common scourges of heart disease and cancer but also much more rare genetic conditions as well.

And indeed, drugs that Moderna has developed are currently in trials for all these types of diseases. Bancel told Bloomberg Businessweek in an interview that the Massachusetts company can also become a dominant force in the vaccine market, developing shots for emerging viruses such as Nipah and Zika, as well as HIV.

Over 50 new viruses that affect humans have been discovered over the past 40 years, and only three of these, incredibly, have authorized vaccines to prevent them — creating fertile ground for minds such as Bencel’s.

“We are going to totally disrupt the vaccine market,” the French entrepreneur, who has a masters degree in engineering and an MBA from Harvard Business School and who worked for Eli Lilly, declared to interviewers.

Bancel illustrates the difficulties and the opportunities posed by the pandemic, with a white board charting the efficacy of his vaccine against the multiple waves of a pandemic.

Booster shots will boost the bottom line for Pharma firms

One chart shows seasonal waves reoccurring over time, becoming less virulent each year but still posing major problems to society. Yet another chart limns the possible deterioration of a vaccine’s efficacy over time, with mRNA products like Moderna’s starting out with the extremely high efficacy but declining over time.

The message conveyed shows that indeed a booster may be needed — which admittedly is favorable for his firm’s bottom line. With nations such as Israel already getting on the booster vaccine bandwagon, it seems the Moderna CEO is firmly in that camp as well.

“My mother is 72, and she has leukemia,” Bancel explains. “I don’t want her to go through the Fall without a boost.”

The small Cambridge company has produced vaccines for a total of ten different viruses that are either currently undergoing trials or about to start them.

Moderna has created three types of coronavirus booster shots that are already in the middle part of their trials, as well as a shot against the annual flu that started its first human study in July; and game-changing trials of HIV shots will begin later in 2021.

Other viruses that have posed a problem for mankind throughout the ages are also now in Moderna’s sights, including the cytomegalovirus, which spreads through body fluids and is a common cause of birth defects.

One “Supershot” may be all we need to combat respiratory viruses in future

This groundbreaking vaccine will begin its a Phase III trials this year in women who are of childbearing age.

In order to fight other maladies, including respiratory ailments including not only Covid but also the flu and others, Moderna has tasked itself with developing a “supershot,” to be administered routinely at your local pharmacy.

Bancel states expansively “Our goal is to give you several mRNAs in a single shot at your local CVS or GP every August or September.”

However, in normal — i.e., non-Covid — times, it takes a great deal of time to make it through the trials and approval processes for vaccines. The lightning-fast emergency authorization process enjoyed by not only Moderna but all other coronavirus vaccines, during the worst of the pandemic, will not take place for all other vaccines that come down the pike.

This more normal public health practice will not only prove to be more frustrating to Moderna — and undoubtedly its investors — but will also give all its competitors time to develop and put forth their own products.

The normal approval process of the US’ Food and Drug Administration (FDA), requiring longer follow-up periods for data and reviews lasting as much as six to ten months, will again be the norm for Moderna and all other biotech firms that utilize mRNA technology.

The New York-based, century-old Pharma giant Pfizer, with its much smaller German partner BioNTech, quickly established itself as an mRNA manufacturing powerhouse after the December 2020 FDA approval of its product, the first one after the long months of the pandemic.

Pfizer states that it aims to produce 3 billion doses of its vaccine by the end of 2021. The firm has also dominated all foreign distribution of coronavirus vaccines so far, especially those based on mRNA technology.

Novavax Inc., based in Gaithersburg, Maryland, announced on June 14 that its recombinant protein vaccine had proven to be 90% effective in trials of more than 30,000 people in the U.S. and Mexico.

Showing relatively few side effects, the performance of this product were on par with those of the best mRNA-based vaccines.

The more established Pharma giants of Sanofi GlaxoSmithKline are currently in Phase III trials on their own coronavirus vaccine, based on protein, which also could be available to the public by the end of 2021.

SVB Leerink analyst Mani Foroohar told Bloomberg Businessweek that Moderna’s work on developing the Covid vaccine have been “truly breathtaking.” However, at this point it is still unknown if its mRNA-based vaccines will have meaningful advantages when dealing with other viral diseases.

He further states that although the sky appears to be the limit in this groundbreaking new technology, “the revenue opportunity is not.”

Moderna’s mRNA vaccine working well against Delta variant

According to Bloomberg, Moderna has raked in profits amounting to almost $8 billion, with CEO Bancel’s own portion of that, including stock options, coming to approximately  $7 billion, according to the Bloomberg Billionaires Index.

The future looks rosy as the Moderna product appears to be performing well against the  Delta variant, and due to its very nature, it is fairly straightforward for the company to deal with the mutations that crop up, altering the vaccine as needed. “We don’t have to introduce new technology or new processes,” Bancel explains, adding “It’s exactly the same thing.”

Bancel tells interviewers that he told his wife before he joined Moderna that there was only a 5% chance the concept of using mRNA to treat illnesses would succeed; however, if it did, the impact would be enormous. He faced a similar uphill struggle when telling Stephen Hoge, now the president of Moderna, about the groundbreaking idea.

Hoge admits that at the time, his reaction amounted to “He’s either brilliant or crazy.”

Hoge, a physician, says that he was interested in being involved in a venture that would have a great societal impact. He eventually signed on to Bancel’s concept, saying that if practicable, it was “really going to transform medicine.”

Much of the success of Moderna’a and Pfizer’s mRNA vaccines are due to their much faster production. Many vaccines against annual influenza are produced inside chicken eggs; meanwhile other genetically-engineered vaccines also require growing their viral proteins inside huge vats containing live cells.

In avoiding these steps, mRNA vaccines can be made and re-engineered quite quickly. In addition, so far it appears that making complex vaccines with multiple viral proteins is a much faster process than when manufacturing traditional vaccines.

Barney Graham, the deputy director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases (NIAID), “Everything with mRNA is just simpler.” The NIAID has been closely collaborating with Moderna in recent months.

Groundbreaking technology perfected in 2015 paved way for coronavirus vaccine

“For me, making vaccines that are as simple as possible is the way to go,” he adds. The mRNA vaccines are especially well-suited to use toward fighting viruses, he notes, because they excel at producing the killer T-cells that destroy the cells that have been infected with the virus.

Before the powerful mRNA molecule could be utilized in vaccines, however, it had to have some kind of defense mechanism added to it in order for it to survive being injected into the body. Normally it would be broken down by our own defense systems.

In addition, the enzymes present in our bodies would also have waged war against the foreign mRNA as soon as they encountered it.

Another first was accomplished in this area as well when a protective lipid, or fat, was added in the form of nanoparticles around the mRNA molecules. As Kerry Benenato, a chemist who left AstraZeneca to join Moderna in 2014, says, they created “balls of fat with little bits of RNA mixed in there.”

Benenato was tasked with devising a way for the mRNA to be be carried into cells, staying alive long enough to do its work and then breaking down; the chemistry involved in this was in its infancy and she had very few published scientific papers to go on in her research.

By the year 2015, however, she and the Moderna team had created their groundbreaking technology after coming up on a type of lipid molecules that fit the purpose. Benenato then says “Then it was off to the races,” as the form patented its process and began using it in vaccines.

This process set the groundwork for a coronavirus vaccine to be manufactured starting when Chinese scientists released the coronavirus RNA profile in early January of 2020. By the end of that month, Bancel again encountered incredulity when he asked his head of manufacturing if he could make a billion vaccine doses in 2021.

Bancel notes “He looked at me like I was insane.”

Prior to this year, Moderna had never manufactured more than 100,000 doses of anything in a calendar year. The Trump administration got the ball rolling however, when the US government pledged to pay a staggering $955 million for the necessary vaccine trials and the small-scale production of the product.

However, Bancel says he was initially unsuccessful in persuading any country to pay for full-blown manufacturing of the vaccine. The firm instead opted to raise the princely sum of $1.3 billion in May 2020 in the form of a stock offering to  make the manufacturing of the vaccine a reality.

How is Moderna’s mRNA vaccine made?

Small pieces of DNA called plasmids containing the genetic blueprint for the Covid-19 spike protein are the basis for the vaccine. The spike protein DNA is then synthesized into mRNA using a technique known as in vitro transcription, which is a process that occurs naturally in the nucleus of cells.

Scott Nickerson, a senior vice president of Moderna, says that, incredibly, the mRNA solution can be manufactured in a matter of hours. However, after that, it takes several days to purify the unreacted enzymes and other unneeded material from the product.

The resulting mRNA mixture then goes into a separate set of clean rooms, where workers formulate the vaccine using the protective lipid nanoparticles.

Last year, it took 19 days to create the vaccine; now the process has been ramped up to only ten days before it is shipped out for packaging.

Moderna uses Lonza Group AG to produce most of its European supply at factories in Switzerland and the Netherlands. In another unusual development regarding the normally secretive, and ultracompetitive pharmacological world, Moderna also agreed this year with Sanofi, Samsung Biologics, and Thermo Fisher Scientific to work together to produce enough capacity to cover what Catalent and Spain’s Laboratorios Farmacéuticos Rovi are currently responsible for.

New vaccine for variant produced in 47 days

Bancel says that his previously small firm had been under the gun, competing with the likes of Pfizer from the get-go. Moderna will end up producing 800 million to 1 billion doses this year, but that represents only about one third of what Pfizer and BioNTech will be able to manufacture.

As he explains, Pfizer employed “100 times more people” when the pandemic broke, and it also had existing plants that it could retool for the necessary vaccine production.

Bancel has hired a small army to produce his mRNA vaccine, with the number of employees almost doubling over the past year, to 1,500.

He projects that in 2022, with additional capacity and a meaningful portion of its production devoted to booster shots and pediatric inoculations that use lower dosages, Moderna and its partners could make as many as 3 billion vaccine doses.

This would bring the previously niche company’s production in line with Pfizer and BioNTech’s projected 2022 production of 4 billion inoculations.

With such gigantic improvements in production, along with the potential addition of  the Novavax and Sanofi’s products, and when Johnson & Johnson and AstraZeneca are able to resolve their supply issues, it is possible the the world could have more than enough coronavirus vaccines to go around.

As health experts hope that the virus makes its way out of populations and becomes a more manageable issue over the next few years, Covid vaccine sales may decline — perhaps precipitously.

Morningstar Inc. analyst Karen Andersen says this market could top out at $72 billion worldwide this year, slip to $65 billion in 2022, and plummet to $8 billion a year after that. The extent of the decline will depend on how many people need booster shots, how often, and whether Moderna, Pfizer, and others will be able to raise prices to compensate for a smaller market.

The science on booster shots is still unsettled as of now — it’s not yet clear how often, or even whether, they will be needed at all.

Moderna has three types of boosters in Phase II trials, including a lower-dose version of its existing vaccine, one booster that’s been customized against the beta variant that was first spotted in South Africa, and a third that combines both.

More variations can be added if necessary. The process for the Beta booster went even faster than for the original shot. Design work started on January 22 of this year, with Moderna ultimately switching out some of the chemical “letters” in its original vaccine, so they correspond to the spike protein in the Beta mutation.

Manufacturing began an incredible three days later, and the first trial dose was administered on March 10 — only 47 days in all, compared with the 65 for the main vaccine.

Moderna is already making deals that include potential booster doses, including a June order from the United States government for 200 million additional shots in late 2021 and early 2022.

Hoge says Moderna could combine as many as a dozen or more viral strains in one shot. The goal is a seasonal vaccine that “eliminates the majority of the respiratory viral diseases that we all suffer from,” he says. “The only way that we’re really going to get good, broad population immunity against these respiratory viruses is if we can make it feel like your flu shot.”

To realize its vision, Moderna will have to move quickly while its competitors race against it.  The Pharma giant Sanofi announced in June that it would spend €400 million ($475 million) annually on research into mRNA research. Now that emergency authorizations are unlikely to be granted for future products, possible side effects and convenience of administration will be of the essence.

Moderna is also attempting to eliminate the laborious refrigeration requirements of its current Covid vaccine. Reducing the high rates of fatigue, headache, and muscle pain incurred especially after the final dose of the inoculation is another area of focus. In addition, Moderna is testing lower doses of the product, which could aid in the amelioration of these conditions.

The great adaptability of mRNA’s adaptability lends it to being easier, and faster, in testing out a range of possibilities. Bancel predicts that in just a few years, Moderna could have as many as 60 drugs and vaccines that are either in human trials or nearly ready for them.

It’s just a matter of combining and recombining the pieces of DNA that are already before them, he explains. “We use the same four-letter code” in the development of vaccines and drug treatments, the CEO says. “We can scale the number of products we have in development at a pace that has never been done before.”