AdAlta has changed the structure of its lead therapy candidate for AD-114, for the treatment of pulmonary fibrosis. The new product, renamed AD-214, has enhanced activity and improved stability compared to AD-114, allowing a better outcome, according to AdAlta.
AD-214 retains key features of its precursor, as it combines two AD-114 molecules with part of the human antibody’s structure, the Fc fragment. This will increase the ability of the recombinant antibody to bind to its target while extending its stability in the body.
“AD-214 will ultimately be of greater benefit to future patients and potential commercial partners,” Sam Cobb, CEO of AdAlta, said in a press release. “An increased half-life results in significantly less frequent dosing and therefore a more desirable and acceptable outcome for patients leading to greater drug compliance.”
Previous preclinical studies showed that AdAlta’s AD-114, a humanized version of a shark antibody, had the potential to reduce both lung and liver fibrosis in mice. These results supported the decision of the U.S. Food and Drug Administration (FDA) to grant AD-114 orphan drug status in January 2017, a designation that will be retained by AD-214.
“We have been able to leverage all the work done to date on AD-114 in the development of AD-214,” said Robert Peach, PhD, non-executive director of AdAlta. “This means we can make use of our existing strong data package and retain orphan drug status for treatment of idiopathic pulmonary fibrosis.”
Although the structural changes of the drug candidate will delay the clinical development of AD-214, the company expects to advance the new product into a Phase 1 clinical trial in the second half of 2019. Accordingly, AdAlta will focus its efforts on the development of AD-214 and halt the manufacturing of AD-114.
The Phase 1 trial will evaluate the safety of single ascending dose and multiple ascending dose of AD-214 in healthy volunteers. The study will take place in Australia.
“Although the redesign of AD-114 into the new Fc-Fusion molecule AD-214 delays us from entering human clinical trials by around 12 months, AdAlta believes the timeline associated with this new molecule is more than offset by its broader clinical utility in a wider range of fibrotic diseases outside of idiopathic pulmonary fibrosis,” Cobb said.