Cystic fibrosis (CF) is the most common fatal inherited disease in the United States. CF results in mucus buildup in the lungs, pancreas and other organs, and mortality is primarily driven by a progressive decline in lung function. There is no cure for CF.
According to the Cystic Fibrosis Foundation (CFF), the median age at death for patients with CF in the United States was 32.4 years in 2019. This means that half of those deaths occurred before the age of 33 — meaning too many people with CF miss the opportunity to finish school, begin careers, start families, and reach other milestones.
According to the CFF, more than 30,000 patients in the United States and more than 70,000 patients worldwide are living with CF and approximately 760 new cases of CF are diagnosed each year.
CF is caused by dysfunctional or missing CFTR protein. We are developing mRNA therapeutics designed to deliver mRNA encoding fully functional CFTR protein to the lung, resulting in the expression of the functional CFTR protein. mRNA therapeutics have the potential to treat all patients with CF, regardless of the underlying genetic mutation.
Infectious Diseases, including COVID-19
We are currently working with our partner Sanofi Pasteur to develop mRNA vaccines for infectious disease pathogens including SARS-CoV-2, the novel coronavirus responsible for the disease known as COVID-19.
Vaccines work by mimicking disease agents to stimulate the immune system; building up a defense mechanism that remains active in the body to fight future infections. mRNA vaccines offer an innovative approach by delivering a nucleotide sequence encoding the antigen or antigens selected for their high potential to induce a protective immune response. mRNA vaccines also represent a potentially innovative alternative to conventional vaccine approaches for several reasons – their high potency, ability to initiate protein production without the need for nuclear entry, capacity for rapid development and potential for low-cost manufacture and safe administration using non-viral delivery. This approach potentially enables the development of vaccines for disease areas where vaccination is not a viable option today. Additionally, a desired antigen or multiple antigens can be expressed from mRNA without the need to adjust the production process offering maximum flexibility and efficiency in development.
Additional Pulmonary Diseases
Beyond our cystic fibrosis clinical program, our researchers are leveraging our proprietary lung delivery platform to evaluate important targets in additional pulmonary diseases. Preclinical research efforts include discovery-stage programs in primary ciliary dyskinesia (PCD), and pulmonary arterial hypertension (PAH).
Primary ciliary dyskinesia (PCD) is an autosomal recessive genetic condition in which clearance of mucus from the respiratory tract is impaired due to defects in ciliary function. Cilia are tiny, hair-like structures on the cells that line the airways. Mutations in more than 30 genes are known to cause PCD and there are approximately 16,000 diagnosed cases of PCD in the United States. Our goal is to use our mRNA platform to potentially restore ciliary function in the lungs of patients with PCD. We are conducting preclinical studies in multiple PCD genes to demonstrate proof-of-concept and support the selection of a lead PCD program.
Pulmonary arterial hypertension (PAH) is a rare, progressive disorder characterized by narrowing of the small arteries of the lungs resulting in increased blood pressure through the lungs, which can damage the heart. There are approximately 53,000 diagnosed cases of PAH in the United States. In developing an mRNA product candidate for PAH, we intend to use our MRT platform to produce a number of protein targets that could potentially slow the progression of the disease. Preclinical studies are underway to evaluate and validate target proteins for this disease.
Other Rare Diseases
We believe that our MRTTM platform may be applied across a broad array of diseases and target tissues via multiple routes of administration. We are currently undergoing lead identification activities seeking to identify additional potential mRNA therapeutics in the liver. All of these programs are in the discovery stage.