AD-114 is a therapy based on shark antibodies that AdAlta is developing as a treatment for pulmonary fibrosis.
Antibodies are proteins the immune system uses to kill invaders. AD-114Â is a small protein that mimics shark antibodies, the proteins that help keep sharks healthy. It has many advantages over traditional monoclonal antibodies because of its unique structure.
Unique properties of AD-114
Human antibodies are made up of two parts: light chains and heavy chains. Shark antibodies have only heavy chains, which gives them special properties.
Shark antibodies’ shape allows them to bind to a lot of invaders. In addition, the bonds they form with invaders are particularly strong.
AdAlta engineered AD-114 to mimic the shape and size of a shark antibody. It belongs to a class of therapies called i-bodies, proteins that combine the features of small molecules and antibodies.
Because of its small size and shape, it has advantages over other monoclonal antibodies used to treat inflammatory disorders. Its small size makes it especially stable, and its shape allows it to bind to targets that traditional monoclonal antibodies are unable to reach. It is also very specific in pulmonary fibrosis, targeting only cells in fibrotic — or scarred — areas of the lungs while ignoring cells in healthy lung tissue.
How AD-114 works
Chemokine receptor type 4, or CXCR4, is a protein found on the surface of some fibrocytes, cells that produce collagen and proteins that increase inflammation. People with pulmonary fibrosis can have unusually high numbers of fibrocytes with CXCR4 on their surface. And elevated levels of CXCR4 on fibrocytes are correlated with a higher death rate in PF patients.
AD-114 targets fibrocytes with CXCR4. Laboratory studies have shown that AD-114’s binding with CXCR4 generates both anti-inflammatory and anti-fibrotic effects. One study observed that AD-114 prevents inflammatory cells from moving into damaged lung tissue.
AdAlta says AD-114 has the potential to be a first-in-class drug because its mechanism of action is so unique.
AD-114 in clinical trials
AD-114 has yet to be studied in a clinical trial, but evidence from laboratory and animal studies suggests it could benefit those with PF.
On July 8, 2016, AdAlta announced a campaign to obtain financing to support a clinical trial. And on January 18, 2017, it reported that the U.S. Food and Drug Administration had granted orphan drug designation to AD-114. Orphan drug status speeds up the development and approval process of treatments for rare diseases. AdAlta expects to begin Phase 1 trials of by 2018.
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