Therapeutic focus

Epigenetic modulation, the alteration of gene expression without altering genetic material

Cereno has two drug projects based on HDAC inhibition with epigenetic effects – the clinical drug candidates CS1 and CS014. The Company is one of the first to develop treatments for cardiovascular disease through the application of epigenetic modulation. This provides the opportunity to develop safer and more effective treatments for cardiovascular diseases in a complete­ly new way.

Epigenetic modulation can be described as chang­ing gene expression without actually changing the genetic code, which is a new way to treat cardiovas­cular diseases. One of the most common epigene­tic modulators is a class of enzymes called histone deacetylase, abbreviated HDAC. HDACs are found in most cells throughout the body and stimulation or inhibition of these can lead to changes in how an individual's DNA is translated into the production of proteins within the cells. This can affect important cellular mechanisms and thus increase or decrease the risk of disease.

In recent years, epigenetic modulation has played an important role in new treatments for cancer, however, research into the use of epigenetic mod­ulation in cardiovascular disease is just beginning. Scientists have discovered ways to regulate cer­tain disease-causing epigenetic changes as a form of treatment through the use of HDAC inhibitors, among other things. HDAC inhibitors are epigene­tic modulators that have been shown to have a full spectrum of potentially disease-modifying effects, with Cereno being among the first biotech com­panies to exploit its effects for the development of innovative drugs for the treatment of cardiovascu­lar disease.

Around 95% of rare diseases do not have approved treatment

There are approximately 6,000–8,000 rare diseases affecting more than 300 million individuals worldwide. Despite this, approximately 95 percent of these diseases have no approved treatment to offer those affected. There is not even a common global definition of what a rare disease is, but different regions have created their own. In the US, it is considered a rare disease if it affects fewer than 200,000 people, while in Europe the definition is that there should be fewer than 1 in 2,000 people affected.

Rare diseases came to be called 'orphan diseases', i.e. abandoned diseases, because pharmaceutical companies were not interested in developing treatments for a smaller market. In the US, therefore, the 'Orphan Drug Act' was launched to create financial incentives to encourage companies to develop novel treatments for rare diseases.

PAH, pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare disease and a specific form of high blood pressure in the pulmonary circulation. The disease is characterized by an increase in the pulmonary pressure secondary to a thickening of the walls of the pulmonary arteries, i.e. the blood vessels that lead from the right side of the heart to the lungs. This impedes blood flow and causes high blood pressure in the lungs, at later stages local blood clots (so-called thromboses) are also formed.

Globally, the disease affects approximately 10 in 100 000 people. It is a severe, progressive disease with various etiologies that ultimately leads to heart failure and poor lung function. Patients with PAH have a severe prognosis, with inadequate treatment options, with more than 50 percent of patients dying within 5 years with a reduced quality of life throughout the course of the disease. The life expectancy of a person with PAH is about 2.5 years without any treatment, which with current medical interventions can be extended up to 7.5 years.

In most cases, there is no known cause of PAH. There is no cure and most patients die from the right side of the heart eventually giving up.

PAH has a major impact on the individuals' level of functioning and causes shortness of breath, fatigue, chest pains, reduced ability to work, unnatural swelling, fainting and heart palpitations. This has significant implications for a patient's physical, mental, and social well-being.

The global market for PAH drugs is estimated to amount to nearly 12 billion dollars by 2027; among the three central markets, US, EU4 + UK and Japan, the US accounts for 60 percent. There is currently no cure available for PAH with the exception of lung transplantation, which patients are often too serious­ly ill to undergo. The treatments offered today are fo­cused on improving the patient's functional level and involve, at best, a moderate slowing of the disease progression. There is therefore a great need for novel disease-modifying treatments that address the un­derlying causes of PAH that can give patients an in­creased opportunity for an improved and longer life.

Thrombosis, a blood clot forming in deep veins

A dangerous thrombosis occurs when a blood clot blocks a blood vessel and it can occur in many dif­ferent places in the body. There are two different forms of thrombosis: venous thrombosis and arterial thrombosis. Venous thrombosis is when the blood clot blocks a vein that carries blood from the body to the heart, and an arterial thrombosis is when the blood clot blocks an artery that carries oxygen-rich blood from the heart to the body. An occluding thrombosis is a serious complication that contrib­utes to nearly 85 percent of all deaths in cardiovas­cular disease, with heart attacks and strokes being two of the most common complications. Many who have suffered a blood clot are prescribed drug treatment to prevent recurrent blood clots. In some cases, preventive drug treatment is initiated to pre­vent thrombosis even for those who never before suffered a blood clot when the risk is considered to be high in this individual.

Venous thrombosis consists of two types of venous thromboembolism, including the conditions deep vein thrombosis and pulmonary embolism, and stroke prevention in atrial fibrillation. Over 3.5 million cases of venous thromboembolism were diagnosed in 2021 and are considered a significant health burden, claiming over 800,000 lives each year in Europe and the US. The most common forms of arterial thrombosis include ischemic stroke and myocardial infarction, which kill more than one in four people globally. An arterial thrombotic event can also lead to poor blood flow to the extremities, which is a complication of peripheral artery disease. It is more common in the legs than in the arms be­cause atherosclerosis is often found to a greater extent in the legs than in the arms due to higher blood pressure in the legs. About 8 million people, in the US alone, have peripheral artery disease.

Treatment for the prevention of thrombosis is a type of maintenance treatment where medicines are primarily prescribed to prevent recurrent throm­bosis during different treatment periods depend­ing on which type of thrombosis is involved. There are many anti-thrombotic drugs, so-called blood thinners on the market, which are used to prevent the formation of blood clots. These existing drugs have all different mechanisms of action, however, all have the serious and unwanted side effect of an increased risk of bleeding that can cause hospital stays and lead to death.

This is the main reason why anti-thrombotic drugs are not optimally used, but rather underutilized, i.e. not prescribed to all needing it, underdosed or used for a too short time. It is estimated that as many as 40–50 percent of people who would need anti-thrombotic drugs do not receive appropriate treatment. An effective drug without the high risk of bleeding that today's available treatments have is sought-after and could completely change the current approach to thrombosis prevention.