The breakthrough mRNA technology behind the world's first approved COVID-19 vaccines now holds a significant position in the biopharmaceutical pipeline, spanning fields from cancer to rare diseases. As a clinical leader, Moderna is preparing for its next major step.

Moderna currently has48 mRNA programs, spanning from preclinical to Phase III stages, standing out in ahighly competitive field, a field that has beenbrewing for decades. The demand for COVID-19 vaccines—including Pfizer and BioNTech's Comirnaty—served as a 'trial by fire' for mRNA technology, and now Moderna is leveraging these tools to drive a new wave of therapies.

One of Moderna's most prominent mRNA candidates is the individualized neoantigen therapy (INT), developed in collaboration with Merck & Co., targeting patients with high-risk melanoma. The two companies announced in late 2023 the initiation of alate-stage trial, in combination with Merck's blockbuster drug Keytruda, following positive interim results. Additionally, Moderna has launched anotherlate-stage INT study, targeting lung cancer patients, also in combination with Keytruda.

Kyle Holen, Moderna head of development, therapeutics and oncology,
Dr. Kyle Holen, Moderna's head of development, therapeutics, and oncology
Image courtesy of Moderna
 

Dr. Kyle Holen, Moderna's head of development, therapeutics, and oncology, says that for cancer and rare diseases, mRNA may lead the industry in new directions.

Here, we spoke with Holen about how Moderna is translating its COVID-19 vaccine success into a promising mRNA pipeline and expanding into new indications beyond infectious diseases.

This interview has been edited for length and style.

PHARMAVOICE:How has Moderna's success with the COVID-19 vaccine influenced the pipeline or the way your department operates?

KYLE HOLEN:COVID-19 opened the door not only for Moderna but for all companies working on mRNA therapies. It showed the world that mRNA is the next wave of novel drugs, and the 'proof of concept' from COVID-19 has permeated almost everything we do.

"I think we are only scratching the surface of mRNA's potential. I know it's bold, but I believe the cure for cancer will be based on mRNA technology."

Kyle Holen

Head of Development, Therapeutics, and Oncology at Moderna

For example, our cancer program INT uses not only the same mRNA technology as the COVID-19 vaccine but also the same lipid nanoparticles. Because of that, we have safety data from over a billion vaccine recipients. No oncology drug in the world has ever had safety information from a billion patients. The extent to which we have learned and grown as a company from everything we learned during COVID-19 is remarkable.

When can we expect to see the next set of trial results for the INT program, and ultimately, approval?

We have now initiated two randomized pivotal Phase III studies, one in melanoma and one in lung cancer. We hope to start more studies in 2024, and we are currently in discussions with regulators about the data packages that would support a potential marketing authorization or approval. We don't have specific dates or timelines—our only mission is to help melanoma patients as quickly as possible. So, we are doing our best to bring what we believe is a truly effective drug to patients as soon as we can. We are working with regulators and our co-development partner Merck to move this forward.

Apart from the COVID-19 vaccine, what factors have been holding back mRNA from large-scale commercialization?

There are two factors. First, mRNA is very unstable in the lab. If exposed to air, it degrades; if in the circulatory system, it degrades immediately. Making mRNA stable enough to actually produce a protein is very difficult. That's essentially what we do with mRNA—mRNA itself doesn't directly help patients; rather, it causes cells to translate a protein. It's the protein that actually does the work inside the cell. But mRNA's lifespan is too short for the protein to complete translation.

The other factor is that we need to get the mRNA into cells. All protein translation occurs inside cells. So, you need to have a stable mRNA that can enter cells. At Moderna, we do two things and focus on these two things. First, we create a more stable mRNA that is easier for cells to read and translate into protein. Second, we encapsulate the mRNA in lipid nanoparticles. These lipid nanoparticles not only protect the mRNA but also help it enter cells, where it is released and translated into protein.

Where are we in terms of the timeline of mRNA's role in medicine right now?

I think we are only scratching the surface of mRNA's potential. I know it's bold, but I believe the cure for cancer will be based on mRNA technology.

We have exciting evidence of activity in autoimmune diseases. We have a cardiovascular program that could help heart failure patients. We also have rare disease programs, not to mention the incredible number of vaccines in our pipeline that all seem to be performing well. We currently have 48 different mRNAs in the clinic, but in the next five years, we expect to have nearly 100 mRNAs in the clinic. The pace of expansion may outstrip Moderna's own capacity to scale.

Going from 48 to 100—that's a big leap over Moderna's competitors. How do you decide when to partner and when to compete?

We are fully partnered with Merck. This is not a race with Merck because we are in the same boat and both want it to succeed. If it turns out that the Merck and Moderna team is the fastest to bring the drug to patients, or if it happens to be the BioNTech team that is faster, that's also fine. Because in all cases, no matter who is fastest, the patient always wins. We want to ensure that life-saving therapies reach patients as quickly as possible.

There is a high level of focus within Moderna. Everything we do here is mRNA. When you have that focus, what you can accomplish is incredible, and it enables Moderna to make technological advances that keep it ahead of competitors. We are building a moat between ourselves and other companies that are only dabbling in mRNA research. I firmly believe that with the nearly 100 programs we will have in the next five years, the experience from these programs will further distance us from competitors.

What do you think the competitive landscape for mRNA therapies will look like in the future?

I hope to see a lot of competitors emerge because a rising tide lifts all boats. Someone once asked me, are you worried about biotech companies and everything they are doing with mRNA? Will they beat you? I said, no. I'm actually glad they are succeeding because it shows the world that we are all on the right track. If it were only Moderna, people would think we just got lucky. But when Gritstone, BioNTech, Pfizer, and others all succeed with this technology, people will start to realize it's real. That also adds more weight to the work we are doing at Moderna.

The COVID-19 vaccine was your first commercial product launched under extraordinary circumstances. How will Moderna bring mRNA therapies to market in a more traditional way?

The way we succeeded with COVID-19 will not be the same way we succeed with RSV, flu, INT, or rare disease programs. Each program is unique, and each has unique challenges. We will learn from all these unique programs and challenges to become a company that is well-prepared for all the new programs in our pipeline.