Chronic obstructive pulmonary disease, or COPD, is one of the most common and fastest growing diseases in the world today. COPD is an inflammation of the lungs and airways that makes them narrow. The disease is mostly caused by tobacco smoking, but it can also occur in people who have spent a long time in environments where the air is polluted.
People with COPD often become short of breath when they exert themselves and have less energy in general. Other common symptoms include coughing up mucus and wheezing, rattling or wheezing. Ultimately, the disease impairs the body's ability to oxygenate, which often leads to death.
In 2016 it was estimated 251 one million people around the world carry the disease, which also caused 3 million deaths. This makes COPD the fourth leading cause of death in the world and if the trend continues, the disease is expected to soon reach third place on the list.
In Sweden, it is estimated that between 400 and 000 people have COPD and it is most common in those who have smoked for a long period. It is unusual to see the disease in people under the age of 700, but among long-term smokers, about half have developed COPD by the age of 000.
The most important treatment is to stop smoking.
There is currently no curative treatment for COPD. The damage that has been done to the lungs cannot be healed. Treatment of COPD patients instead involves trying to prevent further deterioration and relieve the symptoms that arise. For this, smoking cessation is the most important measure.
A first step in relieving the symptoms often consists of inhaled bronchodilators, sometimes in combinations. The disease can fluctuate and during worse periods, cortisone is usually used, either via inhaler or as a tablet. In cases where COPD affects oxygenation, oxygen therapy is used.
Asthma increasingly common in the Western world
Asthma is caused by chronic inflammation of the lining of the bronchial tubes, which makes them extra sensitive and narrows. Asthma can be caused by an allergy, which is the most common type of asthma in children. However, cold air, smoke, stress and physical exertion can also cause asthmatic symptoms.
In 2016, approximately 339 million people around the world asthma and the disease is becoming increasingly common in the Western world, both among children and the elderly. What is causing the increase is not fully understood, but allergies, air pollution and certain substances in the workplace are mentioned as possible culprits. In Sweden, between 8 and 10 out of 100 people suffer from some form of asthma.
Just as in the treatment of COPD, combinations of bronchodilators and cortisone are used.
Huge market in growth
Medicines for the treatment of various respiratory conditions account for almost 10 percent of all pharmaceutical sales worldwide, which in 2009 corresponded to a market of more than USD 52 billion. Here, medicines for COPD and severe asthma account for more than half of sales.
For the eight largest markets (USA, France, Germany, Italy, Spain, UK, Japan and Australia) the market was estimated at barely 10 billion USD in 2015 and by 2025 it is expected to be around USD 14,1 billion, which corresponds to an annual growth of 3,6 percent.
Existing drugs are based on old technology
Despite this huge market, airway dilators, both existing and those in development, are largely based on old, already known mechanisms. These are often single-dose combinations of long-acting beta-2 agonists (LABAs) and long-acting anticholinergics (LAMAs), as well as triple combinations with inhaled steroids (ICSs).
It is worth noting that there is no data that clearly shows that reliever drugs actually improve survival in COPD patients. In addition, there is a great need to find new anti-inflammatory drugs to replace the side-effect-laden inhaled steroids.
The only drugs on the market that have taken a new approach in terms of development are Nucala from GlaxoSmithKline and Benralizumab from AstraZeneca, two biologic drugs that target a specific group of COPD patients with so-called eosinophilic pneumonia – a disease condition caused by an elevated number of white blood cells called eosinophils.
New, more effective substance
In other words, there is still room for new drugs for both COPD and severe asthma, a market segment that Lund-based Respirator intends to advance in. The company has been working to develop a drug for the treatment of COPD and severe asthma since it was founded in 1999.
Preclinical studies have shown that the company's previous lead projects within these indications, RESP1000, was more effective than existing drugs in counteracting the underlying mechanisms that create airway problems. Equivalent anti-inflammatory and bronchodilator effects have since been shown for the new substance RESP9000, now combined with an even more advantageous safety profile.
Combination treatment where existing substances don't work
RESP9000 has been shown to provide complete relaxation of small airways isolated from human lung tissue regardless of how they have contracted. This is a fundamental difference from anticholinergic drugs that can only counteract cholinergic-induced airway contraction. Respiratorius research has shown that airway tissue from some patients has a reduced sensitivity to beta-2-stimulating substances but that this type of tissue can still be relaxed by Respiratorius substances. Insensitivity to beta-2 is a known clinical phenomenon and RESP9000 would fill an important need in the market as an adjunctive treatment where current airway dilating drugs do not provide a sufficient effect.
Aiming for a clinic with an improved patent situation
In 2018, Respiratorius submitted a patent application for RESP9000 which, if approved, provides market exclusivity in the applied countries until 2038, giving the company an advantageous competitive situation.
Motivated by the candidate's good preclinical results, favorable safety profile and attractive patent situation, RESP9000 has emerged as Respiratorius' top project in COPD and severe asthma. The aim is now to take the project to clinical development, which would be an important and value-driving milestone for the company.
This means working to complete the preclinical program with toxicological studies in collaboration with leading, certified toxicological laboratories as soon as possible. A project team of experts has been built up and the tox studies are expected to begin and continue during 2021. In parallel, GMP production for phase 1 will be ongoing and work on process and formulation development has already begun. The project is expected to enter phase I during the first half of 2022.
Note that Respiratorius is also developing VAL001 for treatment of diffuse large B-cell lymphoma (DLBCL), a rare and aggressive form of lymph node cancer. The candidate is ready for phase III, for which the company is seeking a partner. Read more about the candidate and its deal potential here.
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