Moderna’s COVID-19 Vaccine Results Are Promising — But…

Company announced good clinical results — but who is Moderna and what is its RNA-based coronavirus vaccine?

1. Moderna’s clinical study results…

Cambridge, Massachusetts based biotech company Moderna announced today (Monday, November 16, 2020) that its SARS-CoV-2 vaccine known as mRNA-1273 was 94.5% effective in preventing COVID-19 in adults during a Phase 3 trial.

Moderna’s study, called COVE, enrolled 30,000 participants who were randomly assigned to two groups. One group received the mRNA-1273 vaccine, the other group received a placebo (an inert substance like saline).

The goal of COVE was to see if the vaccine prevented COVID-19. The study counted how many participants in each group were diagnosed with the disease two weeks after the second dose was administered. COVE also recorded how severe the COVID-19 cases were.

The study reported a total of 95 cases among the 30,000 participants. The placebo group had 90 cases of COVID-19, while the mRNA-1273 vaccine group had 5. These results were deemed highly statistically significant (meaning this result was not likely to be a result of random chance).

There were 11 severe cases of COVID-19, all occurring in the placebo group, and none in the mRNA-1273 group.

2. Who is Moderna…

Moderna is a young biotech company founded in September 2010 to commercialize the modified messenger RNA (mRNA) developed by Harvard stem cell biologist Derrick Rossi. Today, the company’s focus on vaccines is very different from the original intent to commercialize treatments for “high-value targets” such as cardiovascular diseases and cancer. Although the core technology of modified mRNAs remains, Rossi is no longer with the company.

Most of Moderna’s clinical trials targeting high-margin chronic diseases failed. These studies were done in partnership with established drug giant AstraZeneca. So far, no mRNA-based drug has been approved for human use by Moderna or anyone else.

These challenges spurred Moderna to change course in 2014, and focus on vaccines. Vaccines are a notoriously low-margin business that many pharmaceutical companies are loathe to enter.

Moderna’s CEO since 2011 is Stephane Bancel, a French pharmaceutical sales executive who is noted for being tough and secretive. That secrecy has gone far beyond that of normal pharmaceutical companies who, despite a highly competitive industry, share and publish important clinical data for others to review. Bancel and Moderna’s excessive secrecy was called out in a scathing article in the prestigious British journal, Nature.

The behavior of the leadership is relevant and revealing as it sets the stage for the rest of the company.

Aside from a suspicious unwillingness to share data, Bancel is a co-inventor on over 100 Moderna patents, even though Bancel has never worked with RNA and is not a Ph.D. scientist.

Other top Moderna executives behave in questionable manners as well.

Early in the coronavirus pandemic, Moderna announced strong progress with its vaccine on May 18, 2020. The company’s stock rose by 30%. That same day, Moderna’s Chief Financial Officer Lorence Kim bought stock for $3 million and immediately sold it for $19.8 million. The following day, Moderna’s Chief Medical Officer Tal Zaks bought stock for $1.5 million and flipped it immediately for $9.8 million.

Similarly, Moderna’s largest shareholder, the venture capital investor Flagship Pioneering, made $69.5 million on May 21 and 22. The founder of Flagship Pioneering is Noubar Afeyan, who is also co-founder and chairman of Moderna.

In May 2020, Moderna board member Dr. Moncel Slaoui resigned and became Chief Scientist for Donald Trump’s “Operation Warp Speed”. Although Slaoui is taking no salary as Operation Warp Speed Chief Scientist, he retains over $10 million in Moderna stock. The conflict of interest is as jarring as Trump’s own long list of conflicts of interest. Elizabeth Warren called out Slaoui’s conflicts even as Trump’s administration poured $483 million into the company to assist its vaccine trials.

Make no mistake — there are many very good and well-intentioned people working hard at Moderna. However, the company is run by the executive team, and their behavior and personality is the dominant influence on the behavior and personality of the company.

3. What is Moderna’s mRNA technology…

Messenger RNA, or mRNA, is the way gene’s in our cells get the genetic information encoded in the DNA within the nucleus, out into the cell where it is made into protein. It is an essential and core part of how all cells work, from bacteria to humans. This is also why mRNA is so promising and alluring as a potential drug. Many genetic diseases in which the patient’s own DNA is at fault, can theoretically be treated by injecting the correct mRNA.

The promising part of an mRNA vaccine is that it can encode parts of the virus, like the spike protein, which will then trigger the immune response to attack the virus.

There is a core problem with this idea. Viruses caught onto the concept of injecting its RNA into cells very early on, billions of years ago. Now, every cell on Earth has means of detecting and destroying foreign RNA because it knows it is belongs to a virus. Unfortunately for us, that includes RNA intended as a vaccine.

This is where Derrick Rossi, the person who’s technology Moderna is founded on, comes into the story.

In 2010, Rossi published a paper for controlling the fate of cells into stem cells and back, by introducing mRNA. Rossi used a synthetic mRNA modified to overcome these ancient and “innate antiviral responses”.

The modifications Rossi made to the mRNA were to the bases, the letters of the genetic code. There are four letters to the genetic code, abbreviated as A (adenine), C (cytosine), G (guanine), and U (uridine in RNA — T for thymine in DNA).

Rossi modified the C and U into compounds called 5-methylcytidine (5mC) and pseudouridine (psi), respectively. When Rossi used 5mC and psi in his synthetic mRNA, he found that he was able to reduce the cell’s innate immune response.

Here’s the core problem. Although Rossi’s modified mRNA chemistry dampened the cell’s immune response, for this to work in cells Rossi still needed to use interferon inhibitors. Interferons are immune signaling proteins that respond to viruses. So clearly, his cells still saw the modified mRNA as problematic and responded as if they were viruses. The combination of modified mRNA and interferon inhibitors was successful, though.

Variations of Rossi’s modified bases are at the heart of Moderna’s technology. But there is no indication that Moderna ever included interferon inhibitors as part of their therapy, nor that it would work for humans the same way it worked for Rossi’s cells.

4. What does this mean for me and for Moderna…

Unfortunately, we are in the midst of a terrible pandemic. And as of now, cases are accelerating going into winter, and the next few months are going to be very hard for all of us. Many will get sick, and many will die.

We must wear masks, we must distance, and we must avoid indoor gatherings — even now during the holiday season. Especially now.

We do NOT have a vaccine now, despite all the false promises made by Trump and his team. And we likely will not have one soon.

I am a big fan of Dr. Anthony Fauci, and trust his judgment. Yet I am still skeptical that we will have an effective vaccine in 2021.

Moderna may have an effective vaccine on their hands. But based on the past behaviors of their executive team, I do not trust their announcements. And without them sharing and publishing their clinical results, there is nothing for independent reviewers to judge by. Even if they did publish their results, I do not trust their data.

I fundamentally distrust anything associated with Trump’s Project Warp Speed, and any company or executive who so closely associates with the project or the president.

If a thorough review by an FDA headed by a commissioner appointed by Biden, based on complete transparency of methods and data from Moderna, results in an approval later in 2021, I will feel more confident that Moderna’s vaccine is solid.

Without that, I would avoid Moderna’s vaccine (not to mention their stock) like, well, like the plague.