Lassen Therapeutics and researchers at Cedars Sinai Medical Center in California will together investigate the role of the immune signaling protein interleukin-11 (IL-11) in idiopathic pulmonary fibrosis (IPF), and its potential as a target for antibody-based therapies for this disease.
IPF is a chronic lung disease of unknown origin characterized by the stiffening and thickening of lung tissue, which leads to the formation of scar tissue (fibrosis). Lung injury triggers connective tissue cells, called fibroblasts, to transform into myofibroblasts, producing large amounts of proteins that normally make up the network of substances that surrounds and supports cells.
Over time, this excessive protein production results in fibrosis and lung damage.
IL-11 is a member of the IL-6 family of immune signaling proteins, known as cytokines, and is a major driver and mediator of fibrosis. Studies have found IL-11 is elevated in people with IPF and other fibrotic diseases, Lassen noted, and that its production is stimulated by other known pro-fibrotic factors.
Moreover, it has been reported that the gene providing instructions to make IL-11 is highly active during the transition from fibroblasts to myofibroblasts. A study published in 2019 also demonstrated that blocking IL-11 in an IPF mouse model was sufficient to reverse fibrosis in the animals’ lungs.
These findings suggest that blocking IL-11 activity might halt fibrosis in IPF patients, either on its own or in combination with medications that target other pro-fibrotic factors, such as TGF-beta, PDGF, and CTGF.
Using preclinical models of lung fibrosis, scientists in this collaboration aim to investigate the underlying mechanisms of fibrosis, and generate data backing up the therapeutic potential of antibodies targeting IL-11 receptors in IPF.
“Because of its critical role in the initiation and proliferation of fibrotic processes, inhibition of the IL-11 pathway represents a promising mechanism to target with potential treatments for chronic fibrotic diseases,” Mark Barrett, CEO of Lassen Therapeutics, which specializes in developing antibodies as treatments, said in a press release.
“The Cedars Sinai team has developed sophisticated models of lung fibrosis and is an exceptional partner as we continue to elucidate the role of IL-11 in this complex disease and develop compelling proof of principle for this therapeutic approach,” Barrett added.
LASN-01, the company’s lead candidate that is currently in preclinical testing, is a monoclonal antibody designed to target the IL-11 receptor alpha and block the signaling pathway triggered by IL-11. In addition to its potential in treating fibrotic diseases, LASN-01 may be useful for certain types of cancers, since IL-11 is also known to play a key role in tumor growth.
The Cedars Sinai team will be led by Cory Hogaboam, PhD, a professor of medicine at the Women’s Guild Lung Institute, and member of Lassen’s scientific advisory board.
“We are excited to partner with Lassen and explore the effects of monoclonal antibodies that block IL-11 signaling in our models of IPF,” Hogaboam said. “IPF is a progressive disease, and patients need new, more effective treatments. Targeting the IL-11 receptor represents a potential new pathway for therapeutic intervention.”
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