Australian and German companies, AdAlta and XL-protein, have entered into a collaboration to create a long-acting form of AdAlta’s AD-114, an antibody-based treatment for idiopathic pulmonary fibrosis (IPF) and other fibrotic conditions.
According to the agreement, XL-protein will contribute with their PASylation technology, attaching a string of amino acids that prevents a compound from being degraded too rapidly in the body.
AD-114 is what AdAlta refers to as an i-body. This bioengineered type of compound mimics the shape and key stability features of the antigen-binding domain of shark antibodies, turning them into compounds adapted for human use. This gives i-bodies unique features, combining the high specificity of antibodies with the stability seen in small molecules.
Early preclinical studies have indicated that AD-114 has both anti-fibrotic and anti-inflammatory properties, making it an ideal candidate to treat IPF. Prolonging the time AD-114 stays in the body would allow the use of lower and less frequent dosing.
PASylation is an alternative to the commonly used PEGylation, a procedure where a PEG molecule is attached to a drug to extend its half-life. PASylation attaches strings of the three amino acids — Proline, Alanine, and Serine — to a drug by genetic engineering.
The length of the amino acid tail determines how fast the compound is metabolized, which allows scientists to fine-tune a compound’s half-life. The addition of the tail does not impact other bodily processes, and does not give rise to toxic metabolites.
When the three amino acids are attached to a drug that is already a protein, such as AD-114, the compound can be produced by bacteria, offering a relatively fast and inexpensive way of drug production.
“XL-protein is providing a smart, biological approach to enable precise modifications to AD-114 that are designed to prolong its circulation time in the body and therefore window of activity,” Sam Cobb, CEO of AdAlta, said in a press release. “We are excited to be working with the XL-protein team as we aim to progress AD-114 towards the clinic by early 2018.”
Claus Schalper, the CEO of XL-protein, added that preliminary data from experimental animals demonstrated that the half-life of AD-114 was dramatically extended by the addition of the PAS tail.
“We are pleased to report that preliminary data from pilot studies in animal models look promising as this shows that the plasma half-life of AD-114 has been dramatically extended. In terms of manufacturing, this modification is easily incorporated into AD-114, allowing facile scale-up and downstream purification,” Schalper said.