Wnt Is Back in Drugmakers' Sights, but Is It Druggable?

In 2018, Samumed, a biotech company, secured $440 million in funding to progress its clinical pipeline focused on Wnt signaling modulators, reflecting a renewed interest in targeting the Wnt pathway for therapeutic purposes. The Wnt pathway is essential for tissue growth and maintenance, and its dysfunction is linked to various diseases. Samumed's strategy involves eight new targets within Wnt signaling, emphasizing local delivery methods to reduce toxicity, such as injections for osteoarthritis and topical treatments for alopecia. Their leading compound, SM04690, failed to meet the primary endpoint in a phase 2 trial with 455 patients for osteoarthritis, but the company remains hopeful. While Porcupine inhibitors can inhibit all Wnt signaling and have demonstrated toxicity, other companies are investigating Wnt's role in immune system modulation and its potential to enhance immune checkpoint inhibitor therapy. Despite previous setbacks, there is a positive outlook for the future success of Wnt-based treatments.