Rethinking the Treatment of Serious Lung Diseases
Pulmonary Diseases Driven by mTOR Dysregulation
The mechanistic Target of Rapamycin (mTOR) pathway is a central regulator of cell growth, repair and response to stress. In healthy lungs, this signaling pathway helps maintain balance in both the airways and the blood vessels. However, at times, this regulatory network can become uncontrolled and hyperactive, leading to disease.
In pulmonary hypertension (PH), including pulmonary hypertension associated with interstitial lung disease (PH-ILD) and sarcoidosis-associated pulmonary hypertension (SAPH), hyperactive mTOR signaling contributes to inflammation, fibrosis, and vascular smooth muscle cell hyperproliferation and remodeling. This in turn leads to rising pulmonary vascular resistance, declining lung function, and increased strain on the heart.
In bronchiolitis obliterans syndrome post lung transplant (BOS), immune-driven injury and fibrosis cause small airway obstruction, progressive loss of lung function, and irreversible airflow limitation.
The IRulya Approach: LAM-001
LAM-001 is a proprietary, investigational, once-daily inhaled formulation of rapamycin. Its potential as a disease-modifying therapy in pulmonary disease stems from its ability to inhibit mTOR-mediated pulmonary dysfunction.
By dampening aberrant mTOR signaling, LAM-001 is designed to exert three key effects:
- Anti-proliferative | Designed to reduce abnormal cell growth
- Anti-fibrotic | Designed to limit fibrotic remodeling
- Immunomodulatory effects | Designed to modulate immune-driven disease processes
Together, these properties support the investigation of mTOR inhibition in pulmonary diseases characterized by unchecked cellular growth, fibrosis, and tissue remodeling.
Approved therapies remain limited and do not fully address the underlying pathophysiology driving disease progression.
Why Pulmonary Delivery?
LAM-001 is designed to be delivered directly to the lungs and to overcome the limitations of oral rapamycin for treating pulmonary diseases. We believe LAM-001 has the potential to deliver the following potential benefits as compared to oral rapamycin:
- Targeted: LAM-001 is designed for direct lung delivery and higher local exposure.
- The right chemistry: LAM-001 is engineered with specific physical chemical properties for pulmonary delivery for enhanced lung exposure.
- Improved safety profile: Lower systemic exposure is intended to reduce systemic side effects.
- Convenient: Easy-to-use, once-a-day dry powder inhaler (DPI) expected to enhance patient compliance, with no need for blood-level monitoring.
