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Asmacure:
Using nicotinic agonists to treat asthma
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Nicotine is one of the most addictive drugs in the world, reviled as a villain because of its association with smoking and addiction. However, nicotine in freebase form has been proven to have remarkable therapeutic effects and in some cases the ability to alleviate symptoms. The trick has been to find ways to mimic these positive therapeutic effects without the drawbacks of its addictive properties.
In the course of his pulmonology and respiratory practice, internationally recognized pulmonologist Dr. Yvon Cormier was intrigued by the effects of smoking on his patients with pulmonary issues. Specifically he observed that a number of patients in his practice remarked to him that smoking would actually often alleviate their symptoms. Clinical data out at the time suggested that smokers actually had a lower rate of inflammatory disease, including hypersensitivity pneumonitis, a pulmonary disease caused by an increased immune response to inhaled antigens. Recognizing this puzzling association, Dr. Cormier sought to understand the role of nicotine in inflammation and he began studying nicotinic receptors. From his research, he concluded that there were benefits of nicotinic receptor agonists for inflammatory diseases, specifically in treating asthma. Again, the trick would be developing a product that would target nicotinic receptors, but without the side effects or addictive properties of nicotine.
With that in mind, Dr. Cormier founded Asmacure in 2002 with the help of Evelyne Israël Assayag. By 2007, the company had selected its lead compound ASM-024, a novel molecular entity. Almost a decade after the creation of the company, ASM-024 has demonstrated activity in pre-clinical in vitro, ex vivo and in vivo models of inflammation and asthma, including in mice, dogs and human cells and pulmonary tissue in pre-clinical trial. The results from these trials have also suggested that the nicotinic agonists are able to regulate both inflammation and bronchoconstriction, two important components of this disease constituting a new interesting approach for the treatment of asthma.
Martin Driscoll, the newly appointed CEO for Asmacure, explained this exciting technology and what differentiates it from nicotine and potentially from current treatments for asthma.
“We’re optimistic that we may have a unique compound, our molecules are derivatives of nicotinic receptors and are designed specifically not to cross the blood-brain barrier. They are designed to avoid any of the addictive properties and that has been the case thus far in our studies,” he said.
Moreover, Driscoll believes ASM-024 offers new hope for asthma sufferers because it is an entirely new approach to treating the disease.
“There is definitely a need for new therapeutic approaches to the disease as current treatments have hardly changed over the past 10 to 15 years. Many asthma sufferers have to rely on a combination of therapies to control their exacerbations.”
The compound is currently being studied in clinical trials utilizing a solution form. The solution form is a liquid that is delivered via a nebulizer (a device used to administer medication in the form of a mist inhaled into the lungs).
“Currently, we’re studying it in two Phase 2 studies, one in patients with mild asthma, and the other in patients with stable moderate asthma,” said Driscoll while adding that the two proof-of-concept Phase 2 studies are ongoing to assess the anti-infl ammatory, broncho-dilating and broncho-protective properties of ASM-024 administered by inhalation. There is also a thought that a nicotinic receptor agonist compound may have fewer side effects than the currently available standard of care treatment for these patients, namely fi xed-dose combinations of inhaled corticosteroids and long-acting beta agonists.
If the current clinical studies for ASM-024 prove successful, Driscoll said the company will bridge to a dry powder for inhalation formulation. The reason being he said is that the majority of people who are treated for asthma chronically prefer to get their medicine through an easy-to-administer powder.
“At its basic level, dry powder devices are very portable, and can be carried anywhere. The way the powder can be delivered to the patient depends on their own inspiration and they literally inhale it in a matter of seconds. Nebulizers may be becoming more and more portable, but they are usually some kind of motorized device, a little more bulky, more expensive, and typically when you’re delivering something via nebulization it has to be delivered over seven to 15 minutes. The fundamental difference for patients is a matter of convenience. The more convenient for the patient, the more likely they will take their medicine.”
Driscoll further commented that it is very common with respiratory medications to do proof-of-concept studies in a solution form fi rst, because a solution formulation is generally less diffi cult to manufacture and develop than powder formulations.
“It’s all about getting things done quicker. You want to get to proof-of-concept in the clinic as quick as you can and fi gure out whether the compound does what you think it does.”
Driscoll said the company is proud of the fact that the vast majority of its clinical work has been done here in Canada, with the fi rst Phase 2 trial taking place in research centers in Québec, Hamilton and Saskatoon. The second Phase 2 study is also being conducted in centers in Hamilton and Québec.
The company recently had its fi rst meeting with the U.S. FDA with plans to pursue the development of the drug in the U.S. market. This is part of the reason that Driscoll was hired on, his past work experience fi ts in with the company’s current drug development strategy. For example, prior to joining Asmacure, Driscoll was CEO and director of Javelin Pharmaceuticals, before that he ran one of the respiratory businesses for one of the bigger players in the industry, Schering-Plough Corporation. His track record in raising capital for both private and public companies will prove important as the company continues forward with its Phase 2 proof-of-concept studies and prepares for Phase 3.
While his familiarity with investors is an asset, Driscoll believes that investor interest in the drug and the company will come naturally.
“I think investors and potential pharmaceutical company partners are already showing great enthusiasm for this product. They’re very intrigued with the notion of this new mechanism that could have both the anti-infl ammatory and broncho-dilatory properties in the same molecule. It’s also a sizable market as asthma affects eight to 10 per cent of the North American population.”
Driscoll says the end-game is to develop the product to a point where it can be handed off to a larger pharma fi rm.
“It’s not our intent ultimately to become a commercial enterprise with this lead compound, but that said, we have the capital to develop it as far down the road as we need to. But our preference is to pass it along to an established respiratory pharma fi rm who has the global capabilities to maximize the program.”
Should Asmacure fi nd the right partner, the company will continue to focus on the other analogues or other molecules in its pipeline.
“The best way to describe it is our intent is to be a development company in the infl ammatory diseases business.”
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