Last week in Nature
, collaborative data collected in both Australia and the U.S. were published revealing that AD-114, a locally developed molecule, could be a therapeutic option for patients with idiopathic pulmonary fibrosis (IPF).
The next generation antibody, known as an “i-body,” is currently in development by the Australian biotech AdAlta Ltd., and has received orphan drug designation by the U.S. Food and Drug Administration (FDA).
The prognosis of IPF is very poor with a median survival of only 3-5 years. It is a chronic, fibrotic disease, in which the replacement of small air sacs of the lung with fibrotic tissue causes the gradual worsening of dyspnea. The condition is characterized by the irreversible scarring of lung tissue which makes it difficult for patients to breathe.
At present, there are only two therapies approved by the FDA for the treatment of IPF – pirfenidone and nintedanib – both of which are also approved for use in Australia. Neither are curative, but both have been proven to slow disease progression. Both have also seen patients discontinue use due to severe side effects.
At La Trobe University in Victoria, Australia; The Alfred Hospital in Melbourne, Australia; and Cedars-Sinai Institute in Los Angeles, California, researchers from AdAlta discovered that the AD-114 drug selectively targets and binds to a protein expressed at higher levels in patients with IPF known as CXCR4. CXCR4 is believed to contribute to the recruitment of fibrotic cells to the lung, which is assumed to play a role in disease progression.
Should the candidate reach its full potential, it will exhibit the ability to slow migration of diseased fibroblasts and reduce the production of collagen that is often associated with IPF.
Dr Kate Griffiths, La Trobe researcher and biochemist, was one of the first developers of the i-body technology and a co-author on the paper. She says her group is very excited with the research results, as they demonstrate that the i-body can be applied to an area of unmet therapeutic need.
“Our data add to the small but robust and growing body of literature showing that CXCR4 is an important alternative target for treating IPF and other fibrotic diseases,” she said in a press release. “We have been able to show that the i-body AD-114 binds to lung tissue from IPF patients, and that the i-body blocks migration of some of the cells that are implicated in fibrosis without influencing or impacting the healthy cells. In an animal model, we have shown that the i-body has a protective effect on an artificially induced form of lung fibrosis.”
Dr Griffiths believes that the data clearly demonstrates the clinical potential of the i-body as it pertains to IPF, and shows its unabashed potential as a future therapeutic option. AdAlta’s Chief Scientific Officer Mick Foley, an associate professor at La Trobe who co-authored the paper and contributed to the invention of AD-114, said:
“What is most remarkable about our i-bodies is their incredible specificity and affinity with their target, as these data show. Unlike existing treatments for IPF which have an unknown or very broad mode of action, the mechanism of action AD-114 is exquisitely specific and well understood and the new drug could potentially bring the progression of the disease to a grinding halt.”
Clinical trials of AD-114 are expected to begin enrollment in Australia by the fourth quarter of 2018. AdAlta will not be recruiting patients for its first human trial, however; trial recruitment will be handled by health care professionals.
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