An Emotionally Special Milestone

Today marks an emotionally special milestone for me, as a medical oncologist, and for our entire team.  This morning, we announced that we have dosed our first patient in the Phase 1 study of our personalized cancer vaccine, mRNA-4157.  We have an opportunity to advance a medicine that is so novel, so breakthrough, it could truly transform the treatment of cancer.  And that could enable us to help many, many patients more effectively fight this disease – and, for some, even cure it.

A truly personalized medicine
Every patient that comes into a medical oncologist’s office is unique.  Their cancer is different, they themselves are different, their lives are different, the context of their disease is different.  And what a medical oncologist does is try to tailor therapeutic options for the patient.  While our ability to tailor therapeutic options has expanded in the past few years, in reality, that ability has remained fairly limited – until now.   

With our personalized cancer vaccines, we are not merely tailoring available therapeutic options for the patient.  I think of it as delivering on the true promise of personalized medicine – creating an individualized, completely custom-made medicine for each patient, based on the uniqueness of his or cancer.

Three enabling advancements
An advancement like this doesn’t happen overnight, of course.  Many advancements have led to personalized cancer vaccines being even a possibility to pursue.  There are three primary ones.  

• Advancements with our mRNA vaccine technology.

  We have learned that our mRNA can induce strong immune responses from our experience targeting infectious diseases. As we explore the technology, it has become evident that mRNA vaccines have a unique potential to stimulate T cells, because the immunogenic peptides are expressed from within the cells. And T cells are what our immune system uses to identify and deal with cells gone awry.

• Advancements with checkpoint inhibitors.

 In the past few years, as a field, we’ve learned that the immune system can actually recognize cancer as foreign, but the problem is that the T cells are inhibited.  If we can disinhibit them with checkpoint inhibitors, we see that they are able to eradicate cancer.  In other words, the body is enabled to heal itself. However, we only see this in a small proportion of patients.  So, we need to find ways to help more patients’ immune systems recognize cancer as foreign.

• Advancements in genomic sequencing.

For those patients whose immune system can recognize cancer, we now know that what their T cells are actually recognizing are mutations that we refer to as neoepitopes.  These mutations are ‘new’ to the body as they are found on cancer cells but not on healthy cells.  And because cancer cells are genetically unstable, they occur randomly, so that each patient’s tumor harbors a unique set of mutations. 

Combining these three advances with our small batch, rapid cycle manufacturing process, and our in-house bioinformatics expertise, we came to realize that we had not only the opportunity to make a difference - but, in fact, the obligation to do so – by advancing mRNA-based personalized cancer vaccines.

How the vaccine works … in a nutshell
In a nutshell, here’s how our personalized cancer vaccine works. We sequence each patient’s tumor to find all the neoepitopes present on their cancer. We then predict 20 neoepitopes specific to that patient that should trigger the strongest immune response based on their unique immune system and the particular mutations found in their tumor. We then digitally design an mRNA-based vaccine and deliver it to a clinical trial site where it’s administered to the patient.

The goal is simple … and profound: stimulate the immune response for each patient individually so that more patients can benefit from checkpoint inhibitors, because their immune system is stimulated against their own individual cancer.

We are advancing our personalized cancer vaccine in combination with Merck’s, KEYTRUDA®, the industry-leading checkpoint inhibitor. We’re privileged and grateful to have the equally passionate and deeply knowledgeable Merck team as our partner along this journey.

What drives us … every day
We have a truly phenomenal team at Moderna – bold, relentless and incredibly dedicated.  We are not afraid to ask the tough questions, the big ones that make a difference.  And we work collaboratively across the organization with a tremendous sense of urgency and a shared mission to help as many patients as possible, by translating our understanding of and expertise in science, engineering and medicine to address a significant, unmet clinical need.

It took us 18 months from the time we hired our first employee dedicated to this project until we filed the IND with FDA.  That’s a timeline unlike any I’ve ever seen in our industry.  And it’s the same passion and relentless pursuit that, undoubtedly, will continue to drive us as we progress mRNA-4157 through clinical study.

One step closer
With the holiday season approaching, we’ll soon start to see the familiar, annual influx of seasonal greeting cards arrive at our homes and offices.  For the families and caregivers of patients with cancer, though, this season is too often a reminder of the cards not received—of the battles we were not able to win over the past year.  As a physician, my career has been dedicated to winning more of those battles, and I am hopeful that our announcement today brings us a step closer to achieving that.