What is the approach Moderna is taking toward treating inherited metabolic disorders?
 
Inherited metabolic disorders occur when a genetic mutation leads to a missing or dysfunctional version of a protein that is important for metabolism. While certain lifestyle changes, like dietary restrictions, may help alleviate the most severe symptoms, there are no treatments for the underlying genetic cause for many of these disorders.
 
Moderna is working to address this underlying cause by providing new instructions to cells so the body can replace these missing or dysfunctional proteins. These instructions are known as messenger RNA or mRNA. Our cells use mRNA to interpret information passed down through our genes and turns this information into proteins that build or regulate our bodies. Moderna’s approach is to give specially-engineered mRNA to provide new instructions to the protein-making machinery already inside the cell to treat the underlying cause of inherited metabolic disorders and other diseases.
 
The animal data evaluating our mRNA study drug targeting methylmalonic acidemia (MMA) are compelling. We recently published data evaluating our mRNA study drug in mouse models of methylmalonic acidemia (MMA), which were developed at NIH. In other words, in mice that have a form of MMA, our study drug substantially improved survival and led to sustained growth with long-term dosing and no safety concerns were observed.
 
We believe mRNA therapeutics and vaccines have the potential to work beyond what’s possible with today’s small molecules (or pills), biologics and vaccines. As of May 2019, we have 11 programs in clinical studies across different areas such as infectious diseases, immuno-oncology, rare diseases and cardiovascular diseases, and more than 1,000 clinical trial participants have been dosed with our mRNA technology. Some of these programs are being led by our team and others are being developed in collaboration with Merck and AstraZeneca.
 
How is mRNA therapy different than other approaches like gene therapy or gene editing?
 
Helping the body make its own medicine using mRNA sounds like it might be similar to gene therapy or gene editing. While these treatment approaches seek to treat disease through genetic information, they take fundamentally different approaches.
 
Gene therapy and gene editing alter the original genetic information each cell carries. The goal is to produce a permanent fix to the underlying genetic problem by changing the defective gene. 
 
Moderna is taking a different approach to address the underlying cause of MMA and other diseases. mRNA transfers the instructions stored in DNA to make the proteins required in every living cell. Our approach aims to help the body make its own missing or defective protein (in this case, MUT). Unlike gene editing and gene therapy, mRNA technology does not change the genetic information of the cell, and it’s short-acting. It acts like traditional drugs that can be adjusted over time based on the dose and frequency needed. In simple terms, we are working to provide physicians and patients with a “controllable” way to start and manage their therapy over time.
 
What are you most excited about in your role?
 
It’s an exciting time in medical research right now & we’re learning so much about the potential for new approaches to treat the underlying cause of diseases like MMA. The potential to help patients in more meaningful ways motivates me and my colleagues at Moderna every day.
 
Could Moderna’s mRNA therapy apply to other disease areas?
 
Absolutely! The amazing thing about an mRNA platform is that it has the potential for broad applicability. Proteins are the basis of so many functions of the body. If we can provide the right mRNA instructions, we can in theory create a large inventory of proteins the body may need to address a variety of diseases.
 
At Moderna, we’re exploring options to address many disease areas, including developing study drugs to potentially help the body fight cancer, to protect the body against infectious diseases, and, importantly, other rare diseases without treatment options.
 
What do you want the patient community to know?
 
I want the community to know that everyone in my company is committed to partnering with them and listening to them along the way. We want to learn from patients and their families, and we will continue to share our research and findings so you can learn from our work.
 
I am also excited to share that we have two studies we are working on presently, and both are actively enrolling patients. 
 
The latest study that we are eager to share is referred to as the “Phase 1/2 study.” It is designed to evaluate our investigational mRNA therapy, known as mRNA-3704, in patients with MMA who have a MUT deficiency. We are particularly looking forward to learning from this study, because this represents our first rare disease study drug to advance into clinical trials. The study is now recruiting patients and you can click here to learn more about it.
 
The FDA has granted Fast Track Designation to mRNA-3704, which is provided to facilitate development of drugs designed to treat a serious or life-threatening condition and fill an unmet medical need. The program has also received Rare Pediatric Disease Designation by the FDA and Orphan Drug Designation by both the FDA and the European Medicines Agency (EMA).
 
The other study that is open is the MMA and PA Natural History Study or “MaP” study. This has a similar goal of other studies being conducted by the NIH and OAA: it is designed to learn more about the clinical experiences of patients with organic acidemia but does not involve study drugs. Each of these studies asks different questions about these conditions, and participation is greatly needed across all of them.
 
We thank the OAA community for sharing their experiences with us in starting this journey, and we look forward to additional communication as we learn from you and from our clinical trials.
 

From the Summer 2019 OAA Newsletter