A Wnt/β-catenin pathway agonist under development by Surrozen appears to be effective against idiopathic pulmonary fibrosis (IPF) in mouse models, according to new data.
The results, published April 2 in the journal Respiratory Research, are an early signal of a potential new indication for the company’s SWAP technology.
“Current treatments for severe lung disease like IPF aren’t able to regenerate normal, functional tissue,” Yang Li, Ph.D., executive vice president of research at Surrozen, said in a press release. “This work … represents a breakthrough in understanding the role of the Wnt pathway in lung fibrosis and the potential for Wnt mimetics to reduce fibrosis and improve lung function.”
IPF is a condition where scar tissue builds up in the lungs, making it difficult to breathe. It occurs in about 13 to 20 in every 100,000 people globally, most of them between the ages of 50 and 70. IPF is sporadic and doesn’t have a clear cause, though there are a handful of linked gene mutations and known risk factors. The latter include smoking, exposure to wood or metal dust and some drugs such as certain antibiotics, heart medications and cancer therapies.
The Wnt/B-catenin signaling pathway is a group of proteins that are heavily involved in tissue development and maintenance, including in the lungs. Prior to the new study, it wasn’t clear whether activating the pathway was helpful or harmful in IPF, as there was some evidence that genes associated with its activation were elevated in patient tissue samples and mouse models, the researchers noted in the article.
On the other hand, a type of stem cell found in the lungs requires Wnt signaling activity for cell maintenance and renewal, and research in mice suggested that activating the pathway decreases lung inflammation.
After demonstrating in mice that activating the pathway was more beneficial against IPF than suppressing it, Surrozen researchers tested out a molecule called a Wnt mimetic antibody, which mirrors the effects of proteins involved in Wnt pathway signaling. In mice with IPF, twice-weekly injections of the molecule for two and a half weeks decreased lung fibrosis, reduced inflammation and improved lung function compared to controls. The antibody's benefits appeared to come from its activity on several different types of cells, including cells of the alveoli—the tiny air sacs in the lungs—as well as stromal and immune cells.
“Our findings suggest there is great potential for modulating Wnt/B-catenin signaling to treat lung diseases including IPF—a possibility warranting more thorough explanation,” the researchers wrote in the article. They plan to continue to develop Wnt mimics that target specific cell types, which would enable therapies with a lower risk of systemic side effects.
Surrozen’s focus on the Wnt pathway has yielded two candidates so far: SZN-043 for alcohol-associated hepatitis and SZN-413 for retinal disease. The company had also been developing another drug, SZN-1326, for inflammatory bowel disease but halted that program in January due to side effects.
SZN-043 is currently being tested in a phase 1b trial, for which the company may have data in the second half of 2024. For SNZ-413, which is being co-developed with Boehringer Ingelheim, the biotech announced April 1 that it had completed a phase 1a trial and was in the process of initiating phase 1b.