Soquelitinib shows promise in mice as treatment for lung disease in SSc

Therapy also being developed for other autoimmune diseases, cancer by Steve Bryson, PhD | November 26, 2024

​Soquelitinib, Corvus Pharmaceuticals’ immune-modulating investigational oral treatment for autoimmune diseases and certain cancers, reduced the signs and symptoms of lung disease caused by systemic sclerosis (SSc), according to new preclinical data.

Designed to selectively block ITK, an enzyme predominantly found in immune T-cells, soquelitinib suppresses Th2 cells — a type of immune helper T-cells whose activation drives the development of many autoimmune and allergic diseases. At the same time, ITK inhibition promotes the growth of Th1-type helper T-cells, which are required for immunity to infections and tumors.

The treatment’s goal is to prevent lung damage, inflammation, and high blood pressure related to SSc. It’s also being investigated in other autoimmune diseases and cancers associated with T-cells.

“We continue to build evidence that selective ITK inhibition can modulate immune responses for a wide range of immune diseases,” Richard A. Miller, MD, co-founder, president, and CEO of Corvus, said in a company press release.
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Yannick Allanore, MD, PhD, a professor of rheumatology at Université Paris Cité in France, presented the preclinical data as a poster at the American College of Rheumatology Convergence 2024, held in earlier this month in Washington, D.C.

Treatment reduced symptoms of lung disease caused by systemic sclerosis
In SSc, a type of scleroderma, an abnormal immune response triggers the excess production of scar tissue, or fibrosis. This causes damage to the skin and internal organs, including the lungs, kidneys, and heart. Interstitial lung disease, or ILD, marked by lung inflammation and fibrosis, often leads to respiratory failure and is the leading cause of death in SSc.

The abnormal immune response that drives SSc involves the activation of Th2-type helper T-cells and the production of pro-inflammatory immune signaling proteins.

By blocking the activity of ITK, soquelitinib intends to induce healthy Th1 cells and suppress pro-inflammatory Th2 cells, thus preventing lung fibrosis and easing associated symptoms.

In this study, the researchers used Fra-2 mice to test the therapy’s potential for treating SSc-related lung disease.

This preclinical model mimics many SSc features in humans, including systemic, or bodywide, inflammation, fibrosis of the lung, skin, and heart, ILD, and pulmonary hypertension, or high blood pressure in the blood vessels that supply the lungs. These mice also have high levels of Th2 cells.

After seven weeks of oral soquelitinib treatment, Fra-2 mice showed a significant reduction in the infiltration of immune cells and fibrosis in the lungs compared with untreated Fra-2 mice. Treated mice also showed significant improvement in clinical scores of disease severity and reduced signs of pulmonary hypertension — including a drop in blood pressure in the heart’s right ventricle during a heartbeat.

These findings were confirmed in a second mouse model with induced lung fibrosis. In those mice, soquelitinib reduced pulmonary fibrosis and infiltration with Th2 helper T-cells.

“The preclinical findings reported at ACR confirm this potential for immune-mediated fibrotic diseases such as systemic sclerosis,” Miller said. “The data presented from these models provide a strong rationale for soquelitinib and our next-generation ITK inhibitors to be evaluated for these indications.”

Because Th1 induction is required for immunity to tumors, Corvus is also testing soquelitinib in an ongoing Phase 1/1b clinical trial involving people with T-cell cancers. Interim data demonstrated tumor responses in hard-to-treat cases. As a result, the company has launched a Phase 3 study to test the therapy in people with relapsed peripheral T-cell lymphoma, an aggressive blood cancer that affects the lymphatic system.

Soquelitinib also is being investigated in a Phase 1 study in patients with eczema, or atopic dermatitis.