EXECUTIVE SUMMARY - Asmacure, Ltée: A New Mechanism for the Treatment for Asthma

Asthma is a chronic disease affecting 8% to 10% of the population. According to the 2010 Global Strategy for Asthma Management & Prevention, Global Initiative for Asthma (GINA) 2010 report, asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment. Despite the widespread availability of today’s treatment options, there is still a significant medical need as a large number of patients’ exacerbations are uncontrolled. Many patients receive high doses of medication and therefore become less responsive to their treatment over time. Additionally, many patients require combination therapies to completely manage their asthma symptoms, but some patients are hestitant to take the required doses of these therapies because of the potential negative side effects. Many patients with asthma (approximately 50% in the US) experience only intermittent episodes of exacerbations of their disease. These patients have a “mild” form of the disease and can oftentimes be well-controlled with the intermittent or “as needed” use of an inhaled beta agonist or rescue inhaler. The Guidelines for the Diagnosis and Management of Asthma, released by the National Heart, Lung and Blood Institute’s (NHLBI) National Asthma Education and Prevention Program, define mild asthma as a condition in which the patient has few clinical signs or symptoms of asthma, except for occasional episodes of coughing and wheezing no more than one to two times a week. Unfortunately, a growing population of people with asthma experience persistent, intermittent episodes of significant bronchoconstriction, which is defined by GINA as a “tightening of the muscles that surround the airways.” Their disease is a more moderate or severe form. These patients typically require chronic or daily therapies for effective management of their disease. Asmacure Ltée is a biopharmaceutical company based in Québec (QC), Canada, focused on the development of nicotinic receptor agonists for the treatment of asthma and other inflammatory diseases. The company is currently developing a novel, new molecular entity for the treatment of asthma. Asmacure’s compound was the first nicotinic receptor agonist in the clinic for this indication. Specialty Pharma recently interviewed Martin Driscoll, CEO of Asmacure, to discuss the company’s unique, yet practical approach to treating asthma and its core symptoms.

Q: Why is there a need for more asthma treatments?

A: Currently, the main treatments for the chronic management of asthma are fixed-dosed combinations of inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs). These drugs work by providing the dual capabilities of reducing inflammation in the airways and producing bronchodilation in the person with asthma. This makes the airways less sensitive to asthma triggers and allows patients to have better control of their symptoms. Although these fixed-dose combination medications have been shown to be effective for many patients, the chronic administration of inhaled corticosteroids has been associated with a number of potential negative effects, which can make patients hesitant to use them frequently. Moreover, many patients taking these fixed-dose combination products on a chronic basis often find the need for increasing doses over time and/or the addition of other therapeutic modalities for increased efficacy.

Q: What are the most common side effects of inhaled corticosteroids?

A: The most common side effects of inhaled corticosteroids include oral candidiasis (also known as thrush), dysphonia, bronchospasm, poor growth in children, easy bruising, and decreased bone density. Patients taking higher doses of corticosteroids have an increased risk for these side effects. Asmacure’s lead product, ASM-024, acts by a different mechanism than the current standard of care for the chronic maintenance treatment of asthma, which are fixed-dose combination medications. ASM-024 is a nicotinic acetylcholine receptor agonist for the treatment of asthma. Preclinical studies of ASM-024 have indicated the compound may provide the dual clinical capabilities of an antiinflammatory and bronchodilator in a single entity compound. If these potential dual capabilities of ASM-024 are demonstrated safely and effectively in clinical trials and ultimately approved by regulatory authorities, ASM-024 could be the first treatment for asthma that combines the effects of an anti-inflammatory agent with bronchodilation in a single-entity compound and perhaps avoid the potential negative effects of the inhaled corticosteroids and long-acting beta agonists.

Q: How is Asmacure’s lead product, ASM-024, expected to compare to other asthma treatments currently on the market?

A: Asmacure’s scientific approach of using nicotinic receptor agonists for the treatment of inflammatory diseases originated from the very early clinical observation that smokers have a lower incidence of several inflammatory respiratory diseases. Extensive research by Asmacure has demonstrated that activation at the nicotinic receptor sites has a marked inhibitory effect on lung inflammation.

Nicotinic receptor agonists have been seen to have antiinflammatory properties and in some instances, smooth muscle-relaxing effects. Because inflammation and smooth muscle contraction in the airway are the two major components of asthma, nicotinic receptor agonists have the potential to offer asthma sufferers a unique new treatment modality for their disease.

Q: If ASM-024 has the anti-inflammatory properties of nicotine, does it have the addictive properties as well?

A: Because nicotine is addictive and presents a very limited therapeutic potential, it has not been used in any existing asthma tretaments. However, ASM-024 has been specially designed not to cross the blood brain barrier; therefore, it has not been shown thus far to be associated with the same addictive properties as nicotine. ASM-024 contains dimethylphenylpiperazinium (DMPP), one of the numerous nicotinic agonists from natural and synthetic sources commercially available, which is not expected to cross the blood brain barrier and thus not expected to have addictive properties.

Q: Is there clinical data that suggests ASM-024 is safe and effective?

A: ASM-024 has demonstrated activity in preclinical in vitro, ex vivo and in vivo models of inflammation and/or asthma, including in mice, dogs, and human cells and pulmonary tissue. In preclinical studies, ASM-024 demonstrated dual properties in a single entity for the treatment of asthma. The compound was shown to act both as an anti-inflammatory and a bronchodilator.

Utilizing a novel mechanism-of-action, ASM-024 has been tested to date in 99 healthy volunteers in two successful Phase I clinical studies. ASM-024 is currently undergoing two proof-of-concept Phase II studies. These studies are being conducted in patients with both mild and moderate asthma to assess the anti-inflammatory, bronchodilating, and bronchoprotective properties of ASM-024 administered by inhalation. Phase II results are expected to be announced during the fourth quarter of 2011.

Q: Who do you see as Asmacure’s chief competitors?

A: Currently, Symbicort® and Advair® are the major fixeddose combination medications available in the US for the treatment of asthma. Both of these drugs combine a corticosteroid and long-acting bronchodilator into one inhaled medication to chronically manage the asthma patient’s disease. ASM-024 was the first nicotinic receptor agonist to enter the clinic for study as a treatment for asthma. It has not been reported to date whether other nicotinic receptor agonists in development have demonstrated preclinically the dual capabilities of anti-inflammatory properties and bronchodilation.

Q: What would you say to people who are experiencing the symptoms of asthma and may not be happy with their current treatment?

A: Those who currently have asthma, or who have friends or family with asthma, should keep themselves updated on new research developments in this area, such as ASM-024. Many new therapies are in clinical development and could one day provide better asthma relief with fewer adverse effects. Although there is currently no definite date for bringing ASM-024 to market, Asmacure is looking forward to advancing this compound further through clinical development as there are a large number of asthma patients with uncontrolled symptoms who may benefit from treatment modalities that are active at different targets.

Q: Can you tell us more about yourself and how you came to be the CEO of Asmacure?

A: I have had the opportunity to work in the wonderful industry of pharmaceuticals for more than 30 years. My experience in the pharmaceutical industry has included senior roles in general management, commercial operations, and business development for both privately held and publicly traded life science companies.

Prior to being elected CEO of Asmacure, I was CEO and a Director of Javelin Pharmaceuticals, Inc., a publicly traded company focused on the development of acute care pain products, from March 2008 until July 2010, at which point I led the successful merger of the company with Hospira, Inc. Prior to my role with Javelin, I held senior managerial roles at Schering-Plough Corporation, ViroPharma, Inc., and Reliant Pharmaceuticals. During my tenure at Schering-Plough, I spent a significant amount of time as General Manager of Key Pharmaceuticals, the Schering unit responsible for all respiratory products marketed in the US.

Asmacure was founded in 2002 by Co-Founders Yvon Cormier, MD, an internationally recognized pulmonologist, and the company’s current Chief Medical Officer and immunology and inflammation expert Evelyne Israël Assayag, MSc. I was appointed CEO of Asmacure in April 2011 to use my experience in the biopharmaceutical industry to advance the clinical development of the company’s nicotinic receptorbased programs.

I’m delighted to have joined a unique development company with such novel proprietary technology that has the potential to meet significant unmet medical needs and enhance current clinical practice. The science that has been developed by the team at Asmacure is truly impressive. I look forward to closely working with the talented Asmacure team as we lead the company through this exciting time of development and growth.