Therapeutic Focus
Chronic respiratory diseases are the third leading cause of death. 545 million people worldwide, 7.5% of the world's population live with chronic lung disease1.
34 million people in the United States live with chronic respiratory diseases1. These diseases include:
1 GBD 2020
Targeting a silent enemy
Normal mucus protects the respiratory apparatus by trapping undesired elements (dust, pathogens, cell debris, lipids, DNA, and neutrophils) which is cleared by the mucociliary elevator. However, genetic and environmental factors cause mucus overproduction and/or diminished mucociliary clearance in obstructive airway diseases. This leads to mucus build-up and the formation of “Pathological Mucus Plugs" - a mesh-like network of mucin proteins that form thick tenacious mucus plugs that are difficult to clear.
Mucus plugs obstruct airways, cause inflammation, promote infections and lead to irreversible lung and airway damage and increase the risk of respiratory failure.
Mucus plugs reduce the effectiveness of other inhaled therapies.
Our lead program is developing a treatment for an orphan, inherited obstructive airway disease, Primary Ciliary Dyskinesia (PCD).
PCD affects up to 1 million people around the world. PCD is a rare, autosomal recessive multigenic disease involving 50+ casual genes.
Mutation in one or more of these genes results in defects in structure and/or function of the cilia - tiny hairlike projections on the cells that help the body.
Patients with PCD endure lifelong respiratory disease characterized by chronic and debilitating lung, ear and sinus infections leading to permanent damage in these areas. PCD almost always progresses to bronchiatasis with 25% developing respiratory failure.
Genetics
Mutations in 50+ genes can cause defects in the structure and/or function of motile cilia
Casual Gene Mutations
- DNAH5
- DNAH11
- DNAI1
- CCDC 114
- DNA12
+45 other genes
Manifestation
Reduced muco-ciliary clearance, resulting in the formation of mucus plugs and airway blockage...
Consequences
...Triggering a vicious cycle of infections, permanent lung damage, and disease progression
Effective treatments for PCD are a critical unmet need.
“To date, NO pharmacological intervention has been approved for Primary Ciliary Dyskinesia (PCD)"
Currently available therapies approved for
Cystic Fibrosis are not effective in PCD
50+
Mutations in 50+ genes identified as causal
~99%
Cases progress to Bronchiectasis
0
# of drugs approved for PCD indication
1/ 7500 -1/20,000
The global prevalence of PCD in the US and worldwide
25%
PCD patients experience life-threatening respiratory failure, and some require a lung transplant
Current Pipeline
