Continuing to Gain Momentum

September 13, 2017

Stéphane Bancel, Chief Executive Officer, Moderna


2017 is a key inflection point for Moderna on our journey to make mRNA medicines a reality for patients.     

Our big news: major steps forward for our therapeutic modalities …

The first Phase 1 study of an mRNA therapeutic successfully completed, having met both its primary and secondary endpoints. The first Phase 2 study of an mRNA therapeutic to treat cardiovascular disease (CVD) on the horizon. The first cancer patient dosed with an mRNA immuno-oncology therapeutic in a clinical study. The introduction of a new modality to deliver mRNA therapeutics to the liver, enabling us to now go after chronically dosed mRNA therapeutics for rare liver diseases that are undruggable with current approaches. The naming of our first internal rare liver disease program – an mRNA therapeutic to replace a deficient or missing enzyme that causes the serious and often life-threatening disease methylmalonic acidemia (MMA). 

mRNA therapeutics for three distinct therapeutic areas – CVD, cancer, rare liver disease – derived from a single platform technology.    

At face value, using mRNA as a drug to direct the body’s own cells to express proteins to treat a spectrum of diseases has long been an intriguing concept. At the same time, it seemed somewhat implausible given the enormous complexity of getting mRNA into the body.

We have a long way to go.  Our clinical programs are still early.  As I often say, making drugs is hard.  Making mRNA drugs is even harder.

But with the progress we’ve made just since our last corporate update in January, the optimism both within Moderna and with our partners continues to grow.  What’s more, we’re seeing exciting progress across the mRNA space.      

Perhaps this notion of harnessing mRNA as a new class of medicines is not quite so improbable after all.

Committed to advancing vaccines for unmet infectious disease needs …

It’s no secret that we’ve had our first success advancing our mRNA prophylactic vaccines toward and into the clinic.  And we’re very proud of these accomplishments.

We now have nine prophylactic vaccine development candidates (DCs) in our pipeline, five of which are in clinical trials. 

With encouraging human data in hand from our initial proof-of-concept studies, we are taking on increasingly complex prophylactic vaccines, including our cytomegalovirus (CMV) vaccine, and our combination HMPV+PIV3 vaccine.    

Some important facts to keep in mind: CMV is the leading cause of congenital birth defects. HMPV and PIV3 are the second and third most common causes, respectively, of lower respiratory hospitalizations in children, behind RSV.

Currently, there are no approved vaccines for CMV, HMPV or PIV3.

If we are successful in bringing our CMV vaccine and HMPV+PIV3 vaccine to market, we have the potential to help many, many children and families avoid these dangerous viral infections.

Therapeutic vaccines rapidly advancing toward the clinic …

We’re also making significant progress on the therapeutic vaccines front.  We hope to start dosing a Phase 1 study of our personalized cancer vaccine (PCV) this year, which will encode for approximately 20 neoepitopes unique to each patient. NCI will also be conducting a small study of our PCV. 

And we announced a second therapeutic vaccine today – a cancer vaccine DC targeting mutant KRAS antigens that are present in up to 30% of cancers.

mRNA therapeutics franchise now also coming into its own …

With our achievements with our vaccine technology … and the hurdles we have both faced and successfully overcome, we are now poised to make similar, scalable progress on the therapeutics front. 

What’s really gratifying is that our progress in therapeutics is in line with what we’d envisioned early on for Moderna – using mRNA as a drug could have tremendous applicability across many therapeutic areas and unmet needs.

A cardiovascular therapeutic …

AstraZeneca successfully completed a Phase 1 study for mRNA AZD-8601. This is a therapeutic that encodes for VEGF-A. The study met its primary endpoint of safety and tolerability and also demonstrated proof of mechanism as measured by expression of VEGF-A protein in the skin (protein PK).

With the Phase 1 study completed, AstraZeneca is now planning a Phase 2a study of mRNA AZD-8601 in heart failure patients undergoing CABG surgery, and has filed a CTA in Europe for study.

For those of us who saw the earliest animal data out of our platform in 2012 to now see a drug move toward Phase 2 development is extremely exciting. 

Immuno-oncology therapeutics …

We are now dosing cancer patients with relapsed/refractory solid tumor malignancies or lymphoma

in our Phase 1 clinical trial for mRNA 2416, an intratumoral immuno-oncology therapeutic encoding for OX40 ligand.

This study is important for many reasons.  It’s our first oncology trial, our first internally led mRNA therapeutic to enter the clinic, and our first trial to enroll patients versus healthy volunteers.

Immuno-oncology is a major area of investment for us.  There is much more to come as our IND for our personalized cancer vaccine is open, and new DCs are rapidly advancing in our pipeline.

Rare liver disease therapeutics …

Our platform team advanced a novel modality – liver expression of therapeutic proteins.

This is a major achievement and the culmination of years of effort. It enables us to develop therapeutics that have the potential to treat many serious diseases that are not addressable with current drug approaches. We’ll be describing the foundational elements of this research, starting today at our Investor R&D Day, and through scientific articles that are being submitted for publication.

We also are advancing the first of our new development candidates using this new modality – a therapeutics to treat methylmalonic acidemia, or MMA, a devastating and life-threatening rare liver disease.

Opening up this new modality is core to our mission of bringing unprecedented numbers of new therapies to patients. We are unbelievably focused on the research efforts for additional therapies in this important new area.

Pivoting to therapeutic area R&D …

The venture model, which we embarked upon in early 2014, created an opportunity to focus therapeutic area-specific mRNA research and early development. It was the right model for Moderna at the time.  And very helpful given our then stage as a then-preclinical company. 

But we’ve evolved a great deal in the past three years.  And as we continue to simultaneously introduce more and more mRNA medicines into development, and into and through the clinic, we’ve seen increased interdependence between multiple touch points.  We’ve also seen that the venture model isn’t optimal for fostering this interdependence.

Areas of increased interdependence

  • Discovery <--> Platform Research
  • Development Projects <--> Technical/CMC, Non-clinical
  • Common modalities across Therapeutic Areas
  • Need for strong Clinical/Regulatory coordination

So, after much deliberation, we’ve decided to move from a venture-based model to a Therapeutic Area R&D model. 

Our teams will be aligned around three core matrixed therapeutic areas – infectious diseases, immuno-oncology and rare liver diseases. Our President Stephen Hoge, MD, will head up Research/Preclinical, and our CMO Tal Zaks, MD, PhD, will lead Clinical Development.

We believe a Therapeutic Area R&D model will enable us to nurture areas of interdependence.  It will also let us more effectively share clinical learnings across therapeutic areas. And the continued evolution of our platform, coupled with the rapid cycle time in drug research, will allow tighter integration between therapeutic area research teams and the platform research teams.

 

While this new model will change the reporting structure for a small handful of people, we are not eliminating any headcount. We have eliminated one position, but that individual is moving to a new role at Moderna.

One Moderna, One Mission …

Perhaps the biggest change is that we are setting aside our venture structure and names. This is an important step as we move forward as one Moderna, jointly focused on advancing our mission.

I have always been very optimistic about the potential of Moderna to accomplish great things. 

Today that optimism is even more intense as I consider how far we’ve come and what the future may hold for mRNA medicines to impact human health and improve lives.

I look forward to seeing our team’s continued accomplishments as we barrel toward the year’s end.