During any acute airway inflammation attack, an active inflammation response and an appropriately efficient resolution are equally important. Indeed, the inability to strike the fine balance between being protected and overreacting is often the engine to more serious pathologies. The failure to resolve inflammatory immune responses results in chronic inflammatory airway diseases.
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Chronic airway inflammation is a general feature of asthma that affects more than 350 million people worldwide and causes around 400,000 deaths. In the US, asthma is the most common reason for hospital admissions following an emergency department visits. Although inflammation is common to all forms of asthma, mechanisms activating the immune system differ and ways to treat inflammation have to be adapted. While a number of treatments targeting severe eosinophilic asthma have come out over the past decade, there is still no treatment beyond steroids for non-eosinophilic asthma. For this population, hospital visits are frequent and side effects from maladapted treatment options are burdensome. Chronic airway inflammation is also a critical issue in COPD, cystic fibrosis (CF), and bronchopulmonary dysplasia (BPD).

Current strategies to treat these chronic pathologies focus in large part on inhibiting pro-inflammatory pathways systemically. The challenge to such strategies is to effectively shut down part of the immune response without leaving the patients vulnerable to opportunistic pathogens or crippled by side effects. Due to different profiles of inflammatory responses, however, no single strategy has proven itself to be effective for all people, and response rates for existing therapies have generally been poor.

Increasing specificity without sacrificing efficacy is a difficult path to walk.

Alcea Tx focuses on a new path to treat airway inflammation. While most approved medications seek to treat symptoms, the company’s lead monoclonal antibody assets focus on rebalancing the immune system to treat inflammation at its root cause.

In a healthy state, regulatory T-cells (Tregs) have an anti-inflammatory function that ensures an efficient resolution to inflammation. In conditions including asthma, viral infection, and COPD, however, Alcea’s scientific founders recognized that Tregs are dysregulated, leading to the production of pro-inflammatory Tregs which escalate an immune response causing exacerbation of the inflammatory environment and worsening of disease.

Using its lead monoclonal antibodies, Alcea Tx has successfully shown in preclinical models that inhibiting these pro-inflammatory Tregs prevents the development of acute attacks, reduces all markers of inflammation, and slows down fibrosis and collagen disposition.

Alcea Tx’s technology is based on research from the leading lab studying Tregs at Boston Children’s Hospital/Harvard Medical School.

The following diseases are targeted by Alcea’s immune-tolerance restoration technology.

Asthma
Asthma is one of the sharp-raising diseases in urban countries. It affects more than 25 million Americans. This represents 7.7% of adults and 8.4% of children. Asthma causes the medical system in the US more than $56B of yearly costs. The direct costs make up almost $50.1B, of which hospital stays are the largest share. Indirect costs make up $5.9B. The main treatment for asthma has been either dampening of the immune system using corticosteroids, treating some of the main symptoms such as bronchoconstriction by using Beta-agonists, or trying to treat the effector mechanisms by using biologics. These treatments had both low response rates and serious side effects.

Alcea’s technology targets an entirely different pathway. It aims to restore immune tolerance in the lungs and thus to reset homeostasis. Alcea’s lead asset targets Treg cells in order to recover their immuno-suppressive function, maintaining the rest of the immune system functional.

Pulmonary Viral infections
Respiratory diseases and mainly viral infections of the lungs are the third leading cause of hospitalization in the US. One the main reasons is the yearly Influenza virus infections. It affects more than 31.4 million outpatient visits involving 10.6 million patients and 3.1 million days in hospital. The annual medical costs are in excess of $10B, and the disease accounts for more than 40,000 deaths a year. The current medications for Influenza virus infection can protect from mild and moderate cases of the disease while severe cases are poorly treated. Recently, SARS-CoV2 virus has emerged, causing COVID-19 infection affecting different organs, mainly the lungs. While the use of Dexamethasone, a corticosteroid, has helped severe cases, other leads such as Remdesivir or Baricitinib have yet to show consistent positive results. Alcea Tx’s technology has been validated in preclinical mouse models as well as humanized mouse models for H1N1 influenza virus and proved to restore immune tolerance in the lung. Moreover, by restoring the healing activity of the Treg cells, we were able to enhance tissue healing and tissue restoration and thus decrease the incident of the secondary infections considered as the main cause of death for patients on ventilators.We are currently validating our technology in other models for SARS-CoV2 viral infection in anticipation to get our leading asset further into clinics.