Our lead compound EPI-12323 is a once daily, small molecule, inhaled non-glucocorticoid steroid that targets the inflammatory and airway obstruction cascade in the irritated lung. Initial clinical results indicate that EPI-12323 has pronounced anti-inflammatory and bronchodilator activity and does not exhibit any of the classical side effects of glucocorticoid steroids. EPI-12323 does not bind to the glucocorticoid receptor and no adverse effects have been observed on cortisol, bone or androgenic metabolism. In addition, EPI-12323 is effective in reducing airway inflammation and improving airways resistance and compliance and reducing hyperresponsiveness in three preclinical models.
EPI-12323 was identified as a candidate for development in asthma since it is a non-glucocorticoid steroid and due to its ability to delete adenosine pools believed to be important in asthma. EPI-12323 has demonstrated anti-asthma effects in three separate preclinical models of human asthma. Such an extensive evaluation is a part of the Company's strategy to use sophisticated preclinical models to select only those compounds that have the best chance of clinical and commercial success.
The pharmacology profile for EPI-12323 compares favorably to glucocorticoid steroids, and in some cases exceeds the market leading corticosteroid class. Specifically, EPI-12323 exhibits a long duration of action (perhaps once per day treatment) and a pronounced effect on neutrophils. Neutrophils are believed to play an important role in severe asthma cases that result in death, and are also a key effector cell in COPD.
In a Phase II clinical study, EPI-12323 administered daily was safe, well-tolerated and significantly improved pulmonary function and symptoms in mild asthmatics. The key primary clinical endpoint, reduction in the Late Asthmatic Response, achieved statistical significance. The magnitude of protection achieved is considered clinically important in an asthma model used by many investigators to predict future clinical success. EPI-12323 was studied in 24 men with mild asthma in a double-blind, cross-over study design using allergen challenge, which produces a sustained drop in breathing. When given EPI-12323 once daily for five days, patients had fewer asthma symptoms and reported their breathing had significantly improved. The improvement in asthma symptoms was supported by a reduction in rescue medication use and a reduction in nocturnal awakenings.
As a result of EPI-12323's ability to decrease both eosinophilic and neutrophilic inflammation in the lungs, it is also being developed for COPD. By specifically targeting the neutrophilic inflammation, EPI-12323 is expected to reduce the ongoing tissue destruction and improve small airway obstruction in COPD.
Check back soon for updates on Phase II clinical study results in mild-moderate asthma and moderate-severe COPD patients in three dose groups. Over 250 patients have now been safely dosed with EPI-12323.
Epigenesis is continuing its product development efforts by observing a broader asthma population in a Phase II clinical study using its new formulation in an advanced high-efficiency nebulizer device. Epigenesis expects to complete its Phase II clinical study in a broader asthma population in 2007.
The successful development of EPI-12323 as a single agent opens the opportunity to combine it with other known effective agents in asthma, COPD and other respiratory disorders to maximize the compound’s value. Therefore, EPI-12323 is currently being developed in combination with other drug classes for both asthma and COPD. Using one device to deliver two medications permits customization of the drug combination for individual patient symptoms and offers convenience. For COPD patients, the ability to customize therapy represents a novel approach to a very heterogeneous disease. Epigenesis has completed preclinical pharmacology studies combining EPI-12323 with a long acting beta agonist as well as other drug classes, and has filed patent applications for these combinations.
Our expertise in respiratory medicine and respiratory pharmaceutics enables us to streamline early clinical development thereby saving valuable time and resources.
