A Year of Progress Against Rare Diseases

Today, which is recognized as Rare Disease Day, we can be both heartened and energized by where we are compared to a year ago in the battle against diseases for which patients have few, if any, therapeutic options. The fight is not over, but our progress is very real.

What does progress look like?

One short year ago, we had not yet dosed any rare disease patients. But since that time, we’re thrilled to report progress with two rare disease programs in Phase 1 trials and another on the path to the clinic. And we've formed important relationships with investigators and patient communities around the world.

We have dosed patients in the first two groups of our Phase 1/2 Paramount study of our Propionic Acidemia (PA) candidate. PA is an incredibly rare and severe pediatric disease in which the body can’t break down certain parts of proteins and amino acids, which leads to the build-up of toxic chemicals.   

We've administered about 45 doses in patients, and three patients have successfully completed dosing, and it is incredible to see the safety that we have observed so far. We've dosed patients as young as two years old, which is terrific, and we've also dosed patients as old as 26. We’re seeing good tolerability so far with our mRNA, which is an important early step in development. We believe that this year we will potentially see data that will signal how effective this drug could be and if we can go into registrational studies.

Our Phase 1/2 Landmark study to evaluate the safety and pharmacology of mRNA in patients with Methylmalonic Acidemia (MMA), which is a related disease to PA, is ongoing. We've dosed in MMA, and enrollment of the first cohort in our study is now complete. Additional enrollment for other cohorts is expected to begin soon.

Regarding the third disease, we have opened an IND and opened our first sites related to Glycogen Storage Disease Type 1a (GSD1a) and expect to be dosing this year. In this disease, stored glycogen cannot be metabolized into glucose to supply energy and to maintain steady blood glucose levels for the body. There are no approved therapies except cornstarch, which children must get through feeding tubes when they're quite young to avoid life threatening loss of sugar.

For these children, their lives may depend on a functioning alarm clock to wake them and their caregivers when it is time for their next dose of cornstarch. If a dose is missed, the disease can lead to seizures and, in rare instances, even death. Stories like these inspire us to find a new therapy for GSD1a patients.

In research, we are exploring several other rare genetic disorders with the hope that mRNA technology will offer better alternatives to many more patients and families. We will bring these into clinical studies as guided by the safety and effectiveness data from the research labs. And our work in rare diseases doesn't stop with our own therapeutic development. We have established partnerships to address ultra-rare diseases as well.

An example is our new collaboration with the Institute for Life Changing Medicines to develop a new mRNA therapeutic for Crigler-Najjar Syndrome Type 1, or (CN-1), an ultra-rare disease in which the body cannot break down bilirubin, a substance made by the liver. Ultra-rare diseases are always a challenge for our industry given the very small number of patients who could benefit from the medicine. The goal of this innovative partnership is to make an mRNA therapy for the treatment of CN-1 available at no cost to patients and their families.

Just reflecting on this progress, we are so hopeful that mRNA technology can help where there are currently no restorative therapies for these patients. We are energized by the progress we’ve made so far and will stay relentless in doing the best science and bringing it urgently to patients.

We appreciate so much the collaboration with patients, caregivers, scientists, health care providers and the entire Rare Disease community, because it takes us all to successfully navigate the challenging road ahead. But the energy and hope that we feel makes us believe we will progress even further in developing answers for patients in 2022.