Slide 1: INV102 (nadolol)
INV102 (nadolol) A new approach to the treatment of chronic airway disease
Slide 2: Treating the airway: background and rationale
Treating the airway: background and rationale > Existing drugs do an excellent job in opening constricted airways: bronchodilators include b-adrenergic and anti-muscarinic drug classes > Existing drugs do an excellent job in decreasing inflammatory cells in the airway: inhaled corticosteroid (ICS) a
Slide 3: Nadolol franchise: market size, relevance and interconnectedness
Nadolol franchise: market size, relevance and interconnectedness Chronic Obstructive Pulmonary Disease (COPD) is an umbrella term used to describe chronic lung diseases that cause limitations in lung airflow. 3
Slide 4: The "vicious cycle" of chronic inflammatory airway disease
The “vicious cycle” of chronic inflammatory airway disease Inflammation from: - cigarette smoke Increased - chronic infection (C.F.) IL-8 and - allergen, O3 (asthma) beta- + arrestin pathway activity Increased goblet cell Changes in production/ basal cell loss of populations ciliated epithelial cell
Slide 5: Nadolol has unique properties that could treat airway disease
Nadolol has unique properties that could treat airway disease > In cell experiments, INV102 (nadolol): > Blocks the b-arrestin pathway on airway epithelial cell b2 receptors (Lefkowitz) > In animal experiments, nadolol: > Blocks (prevents) or reduces (treats) the increase in goblet cells caused by i
Slide 6: Nadolol could reverse the "vicious cycle" of airway inflammation
Nadolol could reverse the “vicious cycle” of airway inflammation Shown in clinical trial Nadolol DECREASED IL-8 and + beta- arrestin pathway activity DECREASED goblet cell Restoration production/ of ciliated loss of epithelial ciliated Mucous metaplasia found in cells epithelial COPD, asthma and CF
Slide 7: Oral nadolol program: progress and active clinical trials and results
Oral nadolol program: progress and active clinical trials and results Clinical benefits the only drug targeted to address the unmet medical need of mucous metaplasia in the airway targeted as an add-on to existing therapies to make them safer and more effective by reducing mucous production ta
Slide 8: Oral nadolol: phase II smoking cessation study reporting Q315
Oral nadolol: 155 patients phase II smoking cessation study reporting Q315. Leveraging the data: upcoming analysis and reporting Third quarter planned analyses and reporting Fourth Quarter Biomarkers Smoking cessation Combined data > Report on effects of nadolol vs placebo > Report on smoking cessat
Slide 9: Nadolol franchise: progressively de-risked
Nadolol franchise: progressively de-risked oral nadolol inhaled nadolol Data from current Inhaled nadolol is phase II trials in asthma targeted to treat COPD, and smoking cessation Biomarker data asthma and cystic will support the from oral phase II fibrosis. development of oral programs will nadolo
Slide 10: Inhaled nadolol program: progress and clinical development strategy
Inhaled nadolol program: progress and clinical development strategy Clinical benefits once daily dosing directly to the site of injury at 1/100 of the oral dose to mitigate systemic side effects targeted for long term use in COPD, severe asthma and cystic fibrosis as an add-on to existing therap
Slide 11: References
Nguyen LP., et.al., 2011. Complementary anti-inflammatory effects of a β-blocker and a corticosteroid in an asthma model. Arch Pharmacol. 2011: Oct 2; Nguyen, LP, et al. (2008). Am J Respir Cell Mol Biol 38:256-262