CAL-263 – INFLAMMATORY DISEASE

Completed Trials

• Phase 1 trial in normal human volunteers demonstrated CAL-101 was well tolerated with once daily dosing
• Phase 1 placebo controlled allergen challenge trial in rhinitis patients

Mechanism of Action

Targeting the PI3K Delta provides a novel mechanism of action to treat inflammatory disorders including asthma and chronic obstructive pulmonary disease and rheumatoid arthritis.

Clinical Results

CAL-263 has demonstrated favorable pharmcokinetics and safety with once daily oral dosing in a Phase 1 trial in healthy volunteers.

Preclinical Summary

PI3K Delta inhibitors have demonstrated efficacy in preclinical models of allergic airway inflammation including ovalbumininduced allergic inflammation in mice, ovalbumin-induced allergic inflammation in rats, cockroach allergen-induced allergic inflammation in mice and allergen-induced rhinitis responses in ragweed sensitized dogs.

In the ragweed sensitized dog model, CAL-263 demonstrated improved nasal airflow and decreases in histamines, leukotrienes, and prostaglandin D2, all markers of allergic response.

Efficacy in animal models of rheumatoid arthritis with therapeutic dosing has also been demonstrated. Effects include decreased anti-collagen antibody production, improved radiographic score for bone erosion, decreased pro-inflammatory cytokine levels, decreased joint swelling and inflammation and decreased bone erosion and cartilage erosion.