about iCALM therapies

iCALM™: Inhaled Cationic Airway Lining Modulators

iCALM consists of specific cationic salts at precise ratios that alter the biophysical and biological traits of the airway lining to provide broad spectrum host targeted therapeutic benefit, including compromised disease populations. iCALM is designed as a therapy to be delivered in one to two inhalations of dry powder (DP) using existing dry powder inhaler (DPI) technology. iCALM can be used as a monotherapy or in combination with other treatments. It is anticipated that iCALM will be used as a chronic therapy for acute exacerbation control in compromised patient populations, providing therapeutic effect as a pulmonary inflammation controller and prophylactic against respiratory infection. iCALM is protected by a broad IP portfolio including composition and method of use patents.

iCALM clinical safety and efficacy results:

PUR003, a liquid iCALM formulation, has progressed through two Phase 1 trials in healthy normal volunteers (HNV). The first in-human trial demonstrated that administration of single ascending doses were safe and well-tolerated.  PUR003 has also demonstrated safety and tolerability in a Phase 1b blinded, placebo-controlled cross-over trial in asthma patients with secondary biomarker data suggesting a reduction in airway eosinophils. PUR118, a lead DP iCALM formulation, has been tested in Phase 1 trials in HNV and in two Phase !B trials in COPD patients and was safe and well tolerated in both single ascending dose and multiple ascending dose trials. Secondary biomarkers of efficacy in COPD patients showed a dose-responsive reduction in sputum neutrophils and biomarkers.  A Phase 1b study in cystic fibrosis patients.

iCALM mechanism of action (MOA):

iCALM therapies act uniquely through a multifactorial MOA to treat respiratory infection and reduce airway inflammation associated with infection and chronic respiratory disease. Three principle mechanisms have been characterized to date:

- Potent anti-inflammatory activity – iCALM has been shown to reduce airway
inflammation in multiple preclinical models of inflammation that have predictive
value of clinical efficacy. Reduced inflammation is driven by the alteration of
chemokine and cytokine expression in airway cells that leads to reduced
cellular recruitment to the airway.

- Increased mucociliary clearance – iCALM therapies are composed of
osmotically active materials that when delivered to the airways increase the
hydration state of the airway surface liquid. This effect has been shown in
preclinical testing on air-liquid interface epithelial cell cultures and in animal
models of mucociliary clearance where the determined efficacy is equivalent or
greater than other osmotically active therapies. Increased airway hydration
leads to improved mucociliary clearance and improvements in lung health and

- Broad spectrum anti-infective activity – iCALM therapies act against a wide
array of respiratory pathogens to prevent and treat respiratory infections. In the
airway lining fluid (ALF), iCALM therapies activate the assembly of endogenous
proteins into three dimensional matrices, resulting in enhanced barrier function
in the lung and reducing the penetration of pathogens into the lung tissue. This
activity coupled with improved mucus clearance provides broad spectrum
activity against both bacterial and viral pathogens.

iCALM acute exacerbation control:

Through multiple mechanisms of action, iCALM effectively prevents and treats acute exacerbations associated with chronic respiratory disease. iCALM therapies have the potential to prevent exacerbations of inflammatory airway diseases triggered by viral and bacterial respiratory pathogens and allergens. These exacerbations are the most significant driver of morbidity, mortality, cost, and quality of life decrements in patients with COPD, asthma, and cystic fibrosis.

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